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The marine biodiscovery pipeline and ocean medicines of tomorrow
Abstract
Marine organisms possess the capacity to produce a variety of unique and biologically potent natural products for treating human diseases, many of which are currently commercially available or are in advanced clinical trials. Here we provide a short review on progress in the field and discuss a case study of an EU-funded project, PharmaSea, which aims to discover novel products for the treatment of infections, inflammation and neurodegenerative diseases. Research in this sector is opening new doors for harnessing the potential of marine natural products with pharmaceutical properties.
... They are a combination of cosmetics and pharmaceuticals, where bioactive compounds are added to traditional creams, lotions and ointments with the aim of preventing and treating (6; 27; 35). The cosmetic industry is increasingly focused on the search for new molecules and therefore the use of marine natural products is not surprising (6). Microalgae are the source of some of today's most innovative skin care products. ...
... In recent years we all heard about PCR (polymerase chain reaction), used in some Covid tests, but very few will know that the Taq polymerase enzyme, irreplaceable for PCR, was first isolated from the bacterium Thermus aquaticus, in hot springs. Other enzymes from hot springs and marine environments have been reported, such as Pfu, an enzyme from a marine thermophile, Pyrococcus furiosus, is now also used in PCR (6). Under fluorescence microscopy the use of fluorophores allows the chemical localization of cellular components. ...
... LAL, Limulus-Amoebocyte-Lysate, derived from the crab Limulus polyphemus, is used in the form of the LAL test for the sensitive detection of LPS from Gram-negative bacteria. The European Pharmacopoeia prescribes the LAL test to verify the absence of LPS in samples (6). ...
Marine environments are known to be difficult and complex. To survive in hostile environments, living organisms have developed functional and metabolic adaptive mechanisms, which we are still far from knowing and taking full advantage of. Many compounds of marine origin are structurally complex and have unique functionalities, whose potential goes beyond pharmaceuticals, reaching cosmeceuticals, nutraceuticals, biomaterials and energy. Based on knowledge and technical development, cooperation between academia and industry allows for the sustainable use of marine resources. The present survey does not aim to be exhaustive, we intend to have an idea of the present situation and of future prospects.
... Nowadays, dehydrodidemnin B can be artificially synthesized [61], which has elevated it to the status of "drug" in the treatment of different types of cancers in clinical trials (Section 3.6) [70], despite certain reported limitations [71]. ...
... Since 2018, after completing a phase III trial, plitidepsin is currently approved as a therapeutic agent for relapsed/refractory multiple myeloma patients [210]. Interestingly, studies are testing its combination with gemcitabine, sorafenib [211], and dexamethasone [70]. ...
... Currently, plitidepsin is under further clinical trials [70]. The marketed drug is being tested against solid and hematological malignancies such as T-cell lymphoma, leukemia, and prostate cancer [212]. ...
Cancer is currently considered one of the most threatening diseases worldwide. Diet could be one of the factors that can be enhanced to comprehensively address a cancer patient’s condition. Unfortunately, most molecules capable of targeting cancer cells are found in uncommon food sources. Among them, depsipeptides have emerged as one of the most reliable choices for cancer treatment. These cyclic amino acid oligomers, with one or more subunits replaced by a hydroxylated carboxylic acid resulting in one lactone bond in a core ring, have broadly proven their cancer-targeting efficacy, some even reaching clinical trials and being commercialized as “anticancer” drugs. This review aimed to describe these depsipeptides, their reported amino acid sequences, determined structure, and the specific mechanism by which they target tumor cells including apoptosis, oncosis, and elastase inhibition, among others. Furthermore, we have delved into state-of-the-art in vivo and clinical trials, current methods for purification and synthesis, and the recognized disadvantages of these molecules. The information collated in this review can help researchers decide whether these molecules should be incorporated into functional foods in the near future.
... Maintaining optimal glycemic control, which refers to keeping blood sugar levels within a healthy range, is paramount in preventing or delaying the onset and progression of diabetes complications. This underscores the critical need for effective and readily accessible treatment strategies for diabetes management [12]. The vast marine environment harbors a remarkable diversity of life forms, many of which are a treasure trove of bioactive compounds with potential health benefits. ...
... This understanding will pave the way for the development of targeted therapeutic strategies. Combination Therapies [10,12,13]: Investigating the potential benefits of combining marine-derived compounds with existing diabetes medications could lead to more effective and personalized treatment approaches. Large-Scale Clinical Trials: Well-designed, large-scale clinical trials are necessary to confirm the efficacy and safety of marine-derived compounds for diabetes management in diverse patient populations. ...
Welcome to Pharmaceutical Science: Research and Innovation, a comprehensive exploration of the dynamic and ever-evolving field of pharmaceutical science. This book is intended to serve as both a resource and an inspiration for students, researchers, practitioners, and anyone with a keen interest in the development of medications that improve and save lives. The pharmaceutical sciences sit at the intersection of various disciplines, including chemistry, biology, pharmacology, and medicine. This convergence allows for the innovative approaches that are crucial to advancing drug discovery and development. The goal of this book is to provide a detailed yet accessible overview of the current state of research and innovation in pharmaceutical science. The journey of writing this book has been both rewarding and enlightening It has allowed us to delve deeply into the cutting-edge research that is shaping the future of pharmaceuticals. A key theme throughout this book is the importance of innovation. In an era where the pace of technological advancement is accelerating, the pharmaceutical industry must continually adapt and evolve. This book not only examines the current landscape of pharmaceutical research but also looks forward to the emerging trends and technologies that promise to revolutionize the industry. Topics such as personalized medicine, nutraceuticals, drug discovery, phytoconstituents used for different treatments and novel therapeutic approaches are explored in detail, providing readers with a glimpse into the future of pharmaceuticals. This book would not have been possible without the contributions of many individuals. We are deeply grateful to our colleagues, who have shared their insights and expertise, and to the countless researchers whose work has paved the way for the advancements discussed in these pages. Special thanks go to the peer reviewers whose feedback has been invaluable in shaping the final manuscript. To the students and budding researchers who are just beginning their journey in pharmaceutical science, we hope this book serves as a valuable guide and inspires you to push the boundaries of what is possible To the seasoned professionals, we hope it provides new insights and sparks innovative ideas that contribute to your ongoing work. Writing this book has been a journey of discovery and reflection. It has reinforced our belief in the power of scientific inquiry and the critical role of innovation in addressing the health challenges of our time. As you read through these chapters, we encourage you to think about how the principles and discoveries outlined here can be applied to your own work and how you can contribute to the ongoing evolution of pharmaceutical science. Thank you for choosing to embark on this journey with us. We hope you find Pharmaceutical Science: Research and Innovation to be both informative and inspiring, and that it fuels your passion for advancing the field of pharmaceutical science.
... Despite these encouraging developments, the actual and potential value of MGR for marine bioprospecting remains poorly understood. Studies have focused on counting referenced marine species in patents 23 or GenBank 24 , examining sequences in international patent applications [25][26][27][28] or exploring biological compounds for natural product discovery 29,30 . A common aspect to all these studies, however, is their lack of focus on the connection between the actors involved in the use of MGR and the potential sources for natural product discovery. ...
... Marine biotechnology is mainly focused on species that serve as model organisms in basic research and as a backbone in genetic engineering, allowing the creation of new drugs and increasing the efficiency of biotechnological processes for food and energy production, plant agriculture or the invention of new materials 33 . Marine species currently represent a small, but important, share that is used as a source for natural product discovery 7,30 . Unravelling the global scope of economic interest in MGR is a crucial first step towards understanding the value that rests in the biological functions encoded in genetic sequences and pathways to fair and equitable sharing of benefits from its use. ...
Marine bioprospecting, which involves the exploration of genetic and biochemical material from marine organisms, can be used towards addressing a broad range of public and environmental health applications such as disease treatment, diagnostics and bioremediation. Marine genetic resources are important reservoirs for such bioprospecting efforts; however, the extent to which they are used commercially for natural product discovery and the marine sources from which they are derived are not well understood. Here we introduce a comprehensive database of marine genes referenced in patent filings, the Marine Bioprospecting Patent database. It includes 92,550 protein-coding sequences associated with 4,779 patent filings, identified by analysing all relevant records from genetic sequence databases. Three companies alone—BASF, IFF and DuPont—included sequences from 949 species (more than half of referenced species with identified marine origin). Microbial life in the deep sea, a vast and remote biome predominantly beyond national jurisdiction, is already attracting substantial economic interest; the top ten patent holders have all filed marine gene patents referencing sequences from deep-sea life. Our findings provide an updated understanding of the marine bioprospecting landscape, contribute to the sustainable use of marine biodiversity and underscore the need for policymakers to ensure stewardship of deep-sea ecosystems.
... In our opinion, this could be due both to a real necessity of healthy and viable alternatives to animal-derived nutritional products and to the long times required for preclinical and clinical trials, which do not encourage the employment of these commodities as pharmaceuticals. Preclinical and clinical trials to demonstrate the safety and the beneficial effects of microalgal products can last approximately ten years [28]. 2027 [26]. ...
... In our opinion, this could be due both to a real necessity of healthy and viable alternatives to animal-derived nutritional products and to the long times required for preclinical and clinical trials, which do not encourage the employment of these commodities as pharmaceuticals. Preclinical and clinical trials to demonstrate the safety and the beneficial effects of microalgal products can last approximately ten years [28]. ...
Microalgae are currently considered an attractive source of highly valuable compounds for human and animal consumption, including polyunsaturated fatty acids (PUFAs). Several microalgae-derived compounds, such as ω-3 fatty acids, pigments, and whole dried biomasses are available on the market and are mainly produced by culturing microalgae in open ponds, which can be achieved with low setup and maintenance costs with respect to enclosed systems. However, open tanks are more susceptible to bacterial and other environmental contamination, do not guarantee a high reproducibility of algal biochemical profiles and productivities, and constrain massive cultivation to a limited number of species. Genetic engineering techniques have substantially improved over the last decade, and several model microalgae have been successfully modified to promote the accumulation of specific value-added compounds. However, transgenic strains should be cultured in closed photobioreactors (PBRs) to minimize risks of contamination of aquatic environments with allochthonous species; in addition, faster growth rates and higher yields of compounds of interest can be achieved in PBRs compared to open ponds. In this review, we present information collected about the major microalgae-derived commodities (with a special focus on PUFAs) produced at industrial scale, as well genetically-engineered microalgae to increase PUFA production. We also critically analyzed the main bottlenecks that make large-scale production of algal commodities difficult, as well as possible solutions to overcome the main problems and render the processes economically and environmentally safe.
... It is a critical component of Earth's biodiversity and an abundant source of sustenance, yielding nourishment, medicinal resources, and valuable energy reserves. Besides, the ocean plays a pivotal role in Earth's climate regulation, deeply connecting all aspects of human life (Dupont et al., 2023;Jaspars et al., 2016;Jenkins et al., 2023;Tjiputra et al., 2023). Despite the ever-increasing global awareness of the climate, pollution and biodiversity crises, research has shown low levels of understanding of marine environmental issues and awareness of the ocean's impact on our lives (Frick et al., 2004;author(s); Pantò, 2019). ...
Over the past decade, research has stressed the necessity of increasing ocean teaching in formal and informal education by addressing ocean literacy dimensions. Although board games have emerged as an affordable and accessible option for immersive learning experiences, limited empirical evidence demonstrates their effectiveness in enhancing students' understanding of ocean-related concepts. Board games can encourage face-to-face interactions among peers or teams by combining tangible materials with turn-taking modes and promote students’ engagement with multiple aspects of ocean literacy. The present work aimed to develop an augmented reality (AR) game-based educational tool (The Blue Bounty) to inform about the ocean and explore how this could help improve engagement with different ocean dimensions. The development process followed a co-design approach with university students, based on the Design, Play and Experience (DPE) framework. The game was used in an intervention to assess its ability to address six relevant ocean literacy dimensions in a pre/post assessment design. The findings from the game activity show that the research tool has the potential to significantly increase various dimensions, including knowledge acquisition, awareness enhancement, communication skills, attitude formation, activism engagement, and behaviour change, more than a control traditional lecture. Each dimension is impacted differently, highlighting the multifaceted benefits of integrating these activities into formal and informal environments. Additionally, the results suggest that increasing knowledge may have a positive impact on awareness, communication, attitude, activism and the behaviour layer. Discussion includes implications for the development of more engaging environmental educational tools, including the design, implementation, and measurable outcomes.
... Maintaining optimal glycemic control, which refers to keeping blood sugar levels within a healthy range, is paramount in preventing or delaying the onset and progression of diabetes complications. This underscores the critical need for effective and readily accessible treatment strategies for diabetes management [12]. ...
Diabetes mellitus, a chronic condition that may be life-threatening is a huge threat to the
health of people all over the world. Conventional treatments provide only a limited number of
remedies, and they often come with unintended consequences. An exceptional opportunity
for the development of new anti-diabetic medicines that have strong actions and reduced side
effects is presented by the huge marine environment, which has not been investigated to its
full potential. Subsequent metabolites derived from marine creatures are the subject of this
review, which dives into the fascinating world of secondary metabolites and highlights the
many antidiabetic processes and intriguing therapeutic possibilities of these compounds.
The secondary metabolites that are produced by marine algae, sponges, fungus, and
invertebrates are quite varied in terms of their structural composition. These secondary
metabolites include terpenoids, alkaloids, polysaccharides, and polyphenols. One of the
effects that these compounds display is the inhibition of α-glucosidase and α-amylase, as well
as insulin sensitization and antioxidant activity. These compounds interact with critical
targets in glucose metabolism. Phlorotannins, which are found in brown algae can effectively
block α-glucosidase, which in turn delays the absorption of glucose. Sterols generated from
sea stars have been shown to have insulin-sensitizing effects, whereas alkaloids obtained
from fungi are responsible for maintaining glucose homeostasis. Several marine metabolites
have made it to the preclinical and clinical testing stages, demonstrating their potential for
use in the development of anti-diabetic therapies.
... There are various examples where, after a synthesis for the natural product was developed, the compound found use in clinical routine, 40 while others are still being tested. [41][42][43][44] In addition to the patellamides, several structurally similar cyclic peptides show pharmaceutical potential. 45,46 Chemistry and biochemistry of the patellamides ...
Prochloron didemni, an obligate symbiont of certain ascidians (sea squirts found in tropical areas), produces various cyclic pseudo-octapeptides in large quantities. These secondary metabolites have attracted the attention of medicinal chemists and, due to their four azol(in)e and four amide donor groups, coordination chemists have become interested in these molecules. The structures of the metal-free macrocycles and their dinuclear copper(II) complexes are known, and solution equilibria, spectroscopic properties and a range of biologically relevant reactions have been studied in detail. However, until recently, the properties of the patellamides and structures of the copper(II) complexes in living systems have not been known unambiguously. These are reviewed in the present Perspective and, as a result, it now is possible to discuss possible biological functions of these species.
... The potential of ocean ecosystems in the discovery of novel chemicals with pharmaceutical and cosmetic uses has also been mentioned (Jaspars et al. 2016). As new marine natural products are being discovered, it allows the development of new drugs (Costa Leal et al. 2012). ...
Marine fronts are typically associated with relatively sharp changes in temperature and/or salinity and are characterized by their high nutrient concentrations and phytoplankton biomass. Additionally, top-down and bottom-up processes that involve primary production propagate the structure to the entire ecosystem. As we have seen in the previous chapters, the Patagonian shelf-break front (PSBF) shows marine consumers and biogeochemical cycles coupled to its high primary production. For instance, different groups of vertebrates are coupled to primary production through trophic interactions, and the large amount of phytoplankton photosynthesizing constitutes the so-called biological pump capturing CO2 from the atmosphere. The high biological abundance as well as the high rates of the different ecological processes occurring in the PSBF has been suggested to support a higher provision of marine ecosystem services (ES) in comparison with adjacent areas. In this sense, the PSBF can be seen as a hot-spot of ecosystem services. This chapter explores this hypothesis by revisiting the evidence, identifying gaps, and proposing further lines of research.
... A third line of argumentation points to the importance of creating interactions between academic research and corporate activities to strengthen blue economies, including in developing countries 17,[46][47][48] . A few case studies 49,50 provide insights into how such interactions may develop at different stages of typical marine bioprospecting pipelines 51 . Described cases include a bacteria isolated from the deep sea worm Alvinella Pompejana, which was collected by French researchers and later used to develop a face cream 49,52 , and the 'bengamide' molecule, which U.S. American scientists found in a sea sponge from Fiji and which inspired anticancer clinical trials by Novartis 50,53 . ...
Marine genetic resources hold great value for biotechnological innovation and sustainability-oriented research. However, studies indicate that intellectual property rights pertaining to these resources are concentrated in a handful of companies and countries, triggering contentious international debates. This paper highlights an overlooked dimension: the flow of scientific knowledge in the provision and use of marine genetic research. We identified 23,417 scientific studies that use marine genetic sequences, traced patent references to these studies, and revealed provider and user countries. We found that molecular biological research, oftentimes on bacterial species, attracted the most patenting interest. Some countries owned relatively more patents than they provided in science, with the U.S. benefiting the most from available research. Science by developing countries’ researchers saw limited uptake in patents. These findings aim to inform international biodiversity regimes, such as the UN Treaty on Biodiversity Beyond National Jurisdiction (BBNJ), on how to more equitably distribute marine genetic resources’ economic, socio-cultural, and ecological benefits.
... XCELL-30 developed from microalgae acts on cellular turnover in the basal layer of the epidermis, preserving the youthfulness of the skin. Alguronic Acid is a mix of polysaccharides produced by microalgae with significant anti-aging properties (Jaspars et al. 2016). ...
The demand for new alternatives is very high in the cosmetic world and hence it provides a new dimension of opportunities. Marine resources play a pivotal role in the field of cosmetic industry. The macronutrients (proteins, amino acids, carbohydrates, and lipids) and micronutrients (copper, zinc, iron, etc.) are richly present in marine organisms. These ingredients serve properties in photoprotection, anti-aging along with antioxidant potential. Yet more exploration is called for optimization of production and extraction of the active ingredients from marine resources. Also, more research is claimed to ensure the effectiveness and safety of new components for cosmetic applications.
... Besides providing food, either in the form of flora or fauna, it is a storehouse of several genetic resources that can have multiple uses. Several pieces of research showed that various biochemicals can be found in marine floras and faunas that can be effectively utilized in pharmaceutical, cosmetic, beauty, and many other types of products (Jaspars et al. 2016). Many of these products have industrial applications too (Ferrer et al. 2009). ...
Oceanic domains and their vast resources have been long used by humankind for their benefit.
... The trading of marine ornamental fishes also provides livelihood opportunities to many in the world (Townsend 2011). Recent biotechnological advancements have paved the way for recovering several medicinal products, dietary, and health products from ocean-derived resources that have become a part of our daily life consumption (Jaspars et al. 2016). Deep sea bed mining offers an avenue to extract a plethora of minerals, petroleum, and natural gases (Leal Filho et al. 2021). ...
All the oceans of planet Earth are inter-connected and comprise one huge water body. Due to wind-driven forces and thermohaline circulation, all the water molecules get circulated to every nook and corner of this giant water body. However, based on several physical and chemical properties, as well as geomorphological features, marine water bodies can be classified into several smaller dimensions.
... Marine biotechnology is mainly focused on species that serve as model organisms in basic research and as a backbone in genetic engineering, allowing the creation of new drugs, increasing the e ciency of biotechnological processes for food production and energy production, plant agriculture, or the invention of new materials (Khan et al. 2023;Joseph et al., 2020). Marine species currently represent a small, but important, share that is used as a source for natural product discovery (Jaspars et al. 2016;Sigwart et al. 2021). Unravelling the global scope of commercial activity that involves MGR is a crucial rst step towards understanding the value that rests in the biological functions encoded in genetic sequences and pathways to fair and equitable sharing of bene ts from its use. ...
Perceptions that marine bioprospecting will deliver vast commercial benefits have placed ‘marine genetic resources’ at the center of key policy processes yet our knowledge about their importance remains limited. Here, we introduce a novel global database of marine gene sequences referenced in patent filings, the MArine Bioprospecting PATent (MABPAT) Database. It includes 25,682 sequences from 1,092 marine species associated with 3,258 patent filings, identified by analyzing all relevant sequencerecords from INSDC. Microbial life in the deep sea, a vast and remote biome predominantly beyond national jurisdiction, is already attracting significant commercial interest; all of the top 10 patent holders have filed marine gene patents referencing sequences from deep-sea life, and only three companies, BASF, IFF, and DuPont, included sequences from nearly two-thirds of all species. Our findings underscore the need for policymakers to ensure stewardship of deep-sea ecosystems while providing the most updated understanding of the marine bioprospecting landscape.
... Many of the organisms that live in the ocean produce compounds with potential therapeutic value [38]. As a result, the interest in repurposing of these marine-derived compounds as drugs to treat various diseases has grown significantly [39]. Drug repurposing from marine-derived compounds can provide multiple benefits, such as lower timeline and cost of development, as compared traditional drug discovery and development methods. ...
... Minerals and secondary metabolites such as proteins, flavonoids, sterols, esters, acyl lipids, ester, and saturated and unsaturated fatty acids are abundant in diatoms. According to reports, these bioactive substances are effective anti-cancer, anti-bacterial agents, and antioxidant [76][77][78][79][80] . Due to their little growth cycles and high production, diatoms are unicellular photosynthetic organisms that play a significant role in the biogeochemical circulation of silica, carbon, and nitrogen. ...
... In recent years, more attention has been paid to the study of marine organisms as a source of bioactive compounds with valuable contributions in diverse fields such as human health, pharmaceutics, and industrial application [43][44][45]. A great number of marine bioactive compounds identified to date are venoms, coming from cnidarian, whereby these species occupy an important place as a potential source of bioactive compounds [46][47][48]. ...
Millepora alcicornis is a reef-forming cnidarian widely distributed in the Mexican Caribbean. Millepora species or "fire corals" inflict a painful stinging reaction in humans when touched. Even though hundreds of organic and polypeptide toxins have been characterized from sea anemones and jellyfish, there are few reports regarding the diversity of toxins synthesized by fire corals. Here, based on transcriptomic analysis of M. alcicornis, several predicted proteins that show amino acid sequence similarity to toxins were identified, including neurotoxins, metalloproteases, hemostasis-impairing toxins, serin proteases, cysteine-rich venom proteins, phospholipases, complement system-impairing toxins, phosphodiesterases, pore-forming toxins, and L-aminoacid oxidases. The soluble nematocyst proteome of this organism was shown to induce hemolytic, proteolytic, and phospholipase A2 effects by gel zymography. Protein bands or spots on 1D- and 2D-PAGE gels corresponding to zones of hemolytic and enzymatic activities were excised, subjected to in-gel digestion with trypsin, and analyzed by mass spectrometry. These proteins exhibited sequence homology to PLA2s, metalloproteinases, pore-forming toxins, and neurotoxins, such as actitoxins and CrTX-A. The complex array of venom-related transcripts that were identified in M. alcicornis, some of which are first reported in "fire corals", provide novel insight into the structural richness of Cnidarian toxins and their distribution among species. SIGNIFICANCE: Marine organisms are a promising source of bioactive compounds with valuable contributions in diverse fields such as human health, pharmaceuticals, and industrial application. Currently, not much attention has been paid to the study of fire corals, which possess a variety of molecules that exhibit diverse toxic effects and therefore have great pharmaceutical and biotechnological potential. The isolation and identification of novel marine-derived toxins by classical approaches are time-consuming and have low yields. Thus, next-generation strategies, like base-'omics technologies, are essential for the high-throughput characterization of venom compounds such as those synthesized by fire corals. This study moves the field forward because it provides new insights regarding the first occurrence of diverse toxin groups in Millepora alcicornis. The findings presented here will contribute to the current understanding of the mechanisms of action of Millepora toxins. This research also reveals important information related to the potential role of toxins in the defense and capture of prey mechanisms and for designing appropriate treatments for fire coral envenomation. Moreover, due to the lack of information on the taxonomic identification of Millepora, the insights presented here can advise the taxonomic classification of the species of this genus.
... The ocean has provided anti-cancer drugs and other medically useful biocompounds that contribute to human health. Coordinated plans for bioprospecting and pharmaceuticals development are underway in India (Malve 2016) and Europe (PharmSea, a program discussed in Jaspars et al. 2016). People's interactions with a healthy ocean-as tourists, recreationalists, retirees and incomers to coastal communities-have measurable benefits to their health, with the seaside sometimes referred to as a 'therapeutic landscape' (Finlay et al. 2015) or a 'blue gym' (Depledge and Bird 2009 A healthy ocean is critical to stabilising the global climate. ...
People across the world have diverse economic, sociolegal, institutional, social and cultural relationships with the ocean—both its littoral zones and the open sea spaces through which people have traditionally navigated, migrated, fished, traded, played and sought solace, spiritual enlightenment, adventure, material enrichment, social identity, cultural expression, artistic inspiration or good health. These relationships are reflected in formal and informal institutions (polices, laws, social norms) that regulate many of these activities, including those that regulate access to resources. These institutions represent a series of prior claims and rights to the use and enjoyment of the ocean by coastal and maritime societies.
... In caves, where there are animals (such as rodents, reptiles, birds, arthropods, amphibians, and especially bats) that are the reservoirs of viruses in these ecosystems, the contact among microorganisms and animal excrements, which could be composed of some pathogenic virus, promotes the production of antiviral agents by microorganisms [9]. Many of these compounds have no terrestrial analogues and are unique in terms of chemical structure and biological activity [79]. Elucidating the nature of molecular signals, their targets, and the pathways underlying their production is an essential prerequisite for interpreting inter-kingdom communication, adaptive responses, and systems biology [26]. ...
Pristine environments, such as caves, are unique habitats that are isolated from human activity and are exposed to extreme environmental conditions. These environments are rich sources of microbial diversity, and the microorganisms that thrive in these conditions have developed unique survival skills. One such skill is the biosynthesis of secondary metabolites with potential bioactivities, which provide the organisms with a competitive advantage in these extreme environments. The isolation and characterization of microbial strains from the surfaces of pristine cave environments are important for exploring the biotechnological potential of these organisms. These studies can reveal new products with antibacterial, antifungal, anti-inflammatory, antioxidant, and anticancer activities, among others. In addition, the identification of specific compounds responsible for these biological activities can contribute to the development of new drugs and products for sustainable biotechnological applications. Recent developments in genomics, bioinformatics, chemoinformatics, metabolic engineering, and synthetic biology have opened new possibilities for drug discovery, making the exploration of bacterial secondary metabolites more promising. In recent years, several bacteria with bioactive potential have been described, and several compounds with bioactivity have been identified. These findings are essential for the development of new drugs and products for the benefit of society. This paper discusses the potential of microorganisms found in pristine cave surfaces as a source of new metabolites with bioactivity that could have sustainable biotechnological applications. The authors suggest that more research should be conducted in these environments to better understand the microorganisms and the biosynthesis of these metabolites and to identify new compounds and metabolic pathways that could be of interest for the development of new drugs and products. The aim is to highlight the importance of these habitats as a potential source of new bioactive compounds that could be used for sustainable biotechnological applications.
... As terrestrial environments have been extensively studied, the recent studies focus on less frequently explored habitats, such as marine biotopes [10]. These habitats have already shown their potential to shelter unusual organisms favorable to the discovery of bioactive compounds that can be used in the pharmaceutical industry [10][11][12][13][14]. ...
Despite considerable advances in medicine and technology, humanity still faces many deadly diseases such as cancer and malaria. In order to find appropriate treatments, the discovery of new bioactive substances is essential. Therefore, research is now turning to less frequently explored habitats with exceptional biodiversity such as the marine environment. Many studies have demonstrated the therapeutic potential of bioactive compounds from marine macro- and microorganisms. In this study, nine microbial strains isolated from an Indian Ocean sponge, Scopalina hapalia, were screened for their chemical potential. The isolates belong to different phyla, some of which are already known for their production of secondary metabolites, such as the actinobacteria. This article aims at describing the selection method used to identify the most promising microorganisms in the field of active metabolites production. The method is based on the combination of their biological and chemical screening, coupled with the use of bioinformatic tools. The dereplication of microbial extracts and the creation of a molecular network revealed the presence of known bioactive molecules such as staurosporin, erythromycin and chaetoglobosins. Molecular network exploration indicated the possible presence of novel compounds in clusters of interest. The biological activities targeted in the study were cytotoxicity against the HCT-116 and MDA-MB-231 cell lines and antiplasmodial activity against Plasmodium falciparum 3D7. Chaetomium globosum SH-123 and Salinispora arenicola SH-78 strains actually showed remarkable cytotoxic and antiplasmodial activities, while Micromonospora fluostatini SH-82 demonstrated promising antiplasmodial effects. The ranking of the microorganisms as a result of the different screening steps allowed the selection of a promising strain, Micromonospora fluostatini SH-82, as a premium candidate for the discovery of new drugs.
... Even though discoveries of potential marine-derived therapeutics have been steadily increasing since the advent of SCUBA diving gear in the 1950's, the number of marine natural products that are under development or marketed as approved drugs are rather few. This can mainly be attributed to difficulties in collecting source organisms, challenges for large-scale production of marine natural products, high potential toxicity of numerous marine compounds, and the lack of scalable extraction procedures resulting in limited quantities insufficient for high-throughput bioassays and subsequent developments [9]. ...
The proprotein convertase subtilisin kexin type 9 (PCSK9) emerged as a molecular target of great interest for the management of cardiovascular disorders due to its ability to reduce low density lipoprotein (LDL) cholesterol by binding and targeting at LDLR for lysosomal degradation in cells. Preliminary studies revealed that pseurotin A (PsA), a spiro-heterocyclic γ-lactam alkaloid from several marine and terrestrial Aspergillus and Penicillium species, has the ability to dually suppress the PCSK9 expression and protein–protein interaction (PPI) with LDLR, resulting in an anti-hypercholesterolemic effect and modulating the oncogenic role of PCSK9 axis in breast and prostate cancers progression and recurrence. Thus, a preliminary assessment of the PsA acute toxicity represents the steppingstone to develop PsA as a novel orally active PCSK9 axis modulating cancer recurrence inhibitor. PsA studies for in vitro toxicity on RWPE-1 and CCD 841 CoN human non-tumorigenic prostate and colon cells, respectively, indicated a cellular death shown at a 10-fold level of its reported anticancer activity. Moreover, a Western blot analysis revealed a significant downregulation of the pro-survival marker Bcl-2, along with the upregulation of the proapoptotic Bax and caspases 3/7, suggesting PsA-mediated induction of cell apoptosis at very high concentrations. The Up-and-Down methodology determined the PsA LD50 value of >550 mg/kg in male and female Swiss albino mice. Animals were orally administered single doses of PsA at 10, 250, and 500 mg/kg by oral gavage versus vehicle control. Mice were observed daily for 14 days with special care over the first 24 h after dosing to monitor any abnormalities in their behavioral, neuromuscular, and autonomic responses. After 14 days, the mice were euthanized, and their body and organ weights were recorded and collected. Mice plasma samples were subjected to comprehensive hematological and biochemical analyses. Collected mouse organs were histopathologically examined. No morbidity was detected following the PsA oral dosing. The 500 mg/kg female dosing group showed a 45% decrease in the body weight after 14 days but displayed no other signs of toxicity. The 250 mg/kg female dosing group had significantly increased serum levels of liver transaminases AST and ALT versus vehicle control. Moreover, a modest upregulation of apoptotic markers was observed in liver tissues of both animal sexes at 500 mg/kg dose level. However, a histopathological examination revealed no damage to the liver, kidneys, heart, brain, or lungs. While these findings suggest a possible sex-related toxicity at higher doses, the lack of histopathological injury implies that single oral doses of PsA, up to 50-fold the therapeutic dose, do not cause acute organ toxicity in mice though further studies are warranted.
... La vasta extensión oceánica, con más del 70% de la superficie de nuestro planeta, fue clasificada en la década de 1980, como el mayor reservorio de productos naturales a evaluar para un amplio rango de propiedades biológicas (Gerwick, 1987 (Jaspars et al., 2016;Romano et al., 2017). Los organismos marinos, al evolucionar y vivir en condiciones ecológicas únicas, son capaces de sintetizar moléculas que no tienen equivalencia con las encontradas hasta el presente en los terrestres. ...
Despite the large amount of experimental evidence and the development of some products, to date the vast majority of viral diseases lack therapeutic and prophylactic treatment and continue to be a serious health problem. Several sources have been described as
reservoirs of compounds with antiviral activity against a wide spectrum of viruses. This review
aims to address the research trends on in vitro and in vivo
antiviral effects of marine organisms in recent years, against
different classes of viral pathogens worldwide.
... This number has grown significantly since then. Interestingly, numerous marine leads which are now under clinical trial are promising, and several of these agents are likely to reach the market in the coming years [2][3][4]. Six of ten marine metabolites approved by the FDA are anticancer agents, while three are marine-sponge-derived. Manzamines are a unique class of alkaloids present in marine sponges and possess a fused tetra-or pentacyclic ring system which is linked to a β-carboline moiety. ...
Manzamines are chemically related compounds extracted from the methanolic extract of Acanthostrongylophora ingens species. Seven compounds were identified by our research group and are being characterized. As their biological target is unknown, this work is based on previous screening work performed by Mayer et al., who revealed that manzamine A could be an inhibitor of RSK1 kinase. Within this work, the RSK1 N-terminal kinase domain is exploited as a target for our work and the seven compounds are docked using Autodock Vina software. The results show that one of the most active compounds, Manzamine A N-oxide (5), with an IC50 = 3.1 μM, displayed the highest docking score. In addition, the compounds with docking scores lower than the co-crystalized ligand AMP-PCP (−7.5 and −8.0 kcal/mol) for ircinial E (1) and nakadomarin A (7) were found to be inferior in activity in the biological assay. The docking results successfully managed to predict the activities of four compounds, and their in silico results were in concordance with their biological data. The β-carboline ring showed noticeable receptor binding, which could explain its reported biological activities, while the lipophilic side of the compound was found to fit well inside the hydrophobic active site.
... Natural products (NPs) have been used since ancient times to treat diseases and are the most successful sources of new drug candidates [1,2], with the majority of these being NPs or derivatives of NPs [3,4]. Marine bioprospecting has contributed significantly to the discovery of novel bioactive NPs with unique structures and biological activities, offering alternatives to compounds from terrestrial origin, against which resistance has developed [5]. Marine invertebrate symbionts are particularly promising sources of marine NPs, as the competition between microorganisms associated with invertebrates for space and nutrients is the driving force behind the evolution and production of antagonistic compounds, which often constitute pharmaceutically relevant natural products [6]. ...
Bacterial symbionts of marine invertebrates are rich sources of novel, pharmaceutically relevant natural products that could become leads in combatting multidrug-resistant pathogens and treating disease. In this study, the bioactive potential of the marine invertebrate symbiont Thalassomonas actiniarum was investigated. Bioactivity screening of the strain revealed Gram-positive specific antibacterial activity as well as cytotoxic activity against a human melanoma cell line (A2058). The dereplication of the active fraction using HPLC-MS led to the isolation and structural elucidation of cholic acid and 3-oxo cholic acid. T. actiniarum is one of three type species belonging to the genus Thalassomonas. The ability to generate cholic acid was assessed for all three species using thin-layer chromatography and was confirmed by LC-MS. The re-sequencing of all three Thalassomonas type species using long-read Oxford Nanopore Technology (ONT) and Illumina data produced complete genomes, enabling the bioinformatic assessment of the ability of the strains to produce cholic acid. Although a complete biosynthetic pathway for cholic acid synthesis in this genus could not be determined based on sequence-based homology searches, the identification of putative penicillin or homoserine lactone acylases in all three species suggests a mechanism for the hydrolysis of conjugated bile acids present in the growth medium, resulting in the generation of cholic acid and 3-oxo cholic acid. With little known currently about the bioactivities of this genus, this study serves as the foundation for future investigations into their bioactive potential as well as the potential ecological role of bile acid transformation, sterol modification and quorum quenching by Thalassomonas sp. in the marine environment.
... Micro-algal-derived products are currently successfully produced for use in cosmetics and pharmaceutical products [7]. Examples include cyanobacterial polysaccharides used in personal skincare products and oligopeptides derived from extracts of Chlorella sp., which can promote firmness of the skin [8]. Various drug candidates with anti-inflammatory, anticancer and anti-infective activities have been identified in the pharmaceutical industries [9]. ...
Edible algae, including seaweeds, are a source of functional food, dietary supplements, metabolites and bioactive compounds. Algal-based functional foods have potential health benefits, and their commercial value depends on their applications in the food and nutraceutical industries.
This book covers several aspects of algal-based functional foods. It informs the reader about algal cultivation techniques, environmental impact, habitat, nutraceutical potential, extraction of bioactive metabolites, functional-food composition, bio-prospection, culture-induced nutraceutical compounds, algae-based bio-packaging, algal-biorefinery, toxicity, trends and future prospects.
The editors present the topics in a research-oriented format while citing scholarly references.
This book is a comprehensive resource for anyone interested in the nutritional benefits and industrial utilization of algae as a sustainable food source.
... Therefore, due to these oceanic peculiarities, natural marine products are more robust and bioactive than those of their terrestrial counterparts, thus having a higher chance of drug discovery [34]. The ocean, being the greatest biodiversity on earth, represents a treasure trove of new beneficial natural products [35,36]. These ranges of natural products can be obtained from invertebrates and marine microorganisms. ...
Microbial secondary metabolites are an important source of antibiotics currently available for combating drug-resistant pathogens. These important secondary metabolites are produced by various microorganisms, including Actinobacteria. Actinobacteria have a colossal genome with a wide array of genes that code for several bioactive metabolites and enzymes. Numerous studies have reported the isolation and screening of millions of strains of actinomycetes from various habitats for specialized metabolites worldwide. Looking at the extent of the importance of actinomycetes in various fields, corals are highlighted as a potential hotspot for untapped secondary metabolites and new bioactive metabolites. Unfortunately, knowledge about the diversity, distribution and biochemistry of marine actinomycetes compared to hard corals is limited. In this review, we aim to summarize the recent knowledge on the isolation, diversity, distribution and discovery of natural compounds from marine actinomycetes associated with hard corals. A total of 11 new species of actinomycetes, representing nine different families of actinomycetes, were recovered from hard corals during the period from 2007 to 2022. In addition, this study examined a total of 13 new compounds produced by five genera of actinomycetes reported from 2017 to 2022 with antibacterial, antifungal and cytotoxic activities. Coral-derived actinomycetes have different mechanisms of action against their competitors.
... The marine environment and the organisms living within it are being increasingly exploited as a source of natural defense metabolites and bioactive compounds [1][2][3]. Within marine organisms, jellyfish, particularly scyphomedusae, are raising increasing interest as a source of compounds for biotechnological applications [4][5][6]. Generally considered a nuisance, particularly during their sudden and massive appearances (blooms), because they interfere with human activities at sea along the coasts (e.g., tourism, fisheries and industries) by stinging swimmers, damaging fishing gears and caught fish as well as clogging power plant water inflows [7], jellyfish have been an important part of the diet of eastern populations, particularly the Chinese [8]. ...
Jellyfish are commonly considered a nuisance for their negative effects on human activities (e.g., fisheries, power plants and tourism) and human health. However, jellyfish provide several benefits to humans and are commonly eaten in eastern countries. Additionally, recent studies have suggested that jellyfish may become a source of high-value molecules. In this study, we tested the effects of the methanolic extracts and enriched fractions, obtained by solid-phase extraction fractionation, from the scyphomedusae Pelagia noctiluca, Rhizostoma pulmo, Cotylorhiza tuberculata and the cubomedusa Caryddea marsupialis on different human cancer cell lines in order to evaluate a potential antiproliferative activity. Our results indicated that fraction C from Caryddea marsupialis-(CM) and C. tuberculata oral arms (CTOA) were the most active to reduce cell viability in a dose-dependent manner. LC/MS based dereplication analyses highlighted that both bioactive fractions contained mainly fatty acids and derivatives, with CM additionally containing small peptides (0.7–0.8 kDa), which might contribute to its higher biological activity. The mechanism of action behind the most active fraction was investigated using PCR arrays. Results showed that the fraction C of CM can reduce the expression of genes involved in apoptosis inhibition in melanoma-treated cells, which makes jellyfish a potential new source of antiproliferative drugs to be exploited in the future.
... accessed on 20 November 2020). This is also highlighted by the number of novel secondary metabolites being elucidated per year (1554 in 2018) and a significant number of marine-derived drug candidates under clinical trials or pending approval(Mayer et al., 2010;Hu et al., 2015;Jaspars et al., 2016). Despite the intensive research effort, the marine environment can be considered rather underexplored for prospecting bioactive molecules in comparison with terrestrial ecosystems(Hughes and Fenical, 2010;Santos et al., 2020a). ...
... Microalgae are a huge renewable and eco-friendly source of natural compounds, including vitamins, carbohydrates, pigments, sterols and lipids, presenting several bioactivities for biotechnological applications in the pharmaceutical, nutraceutical and cosmeceutical sectors [1][2][3], such as antiviral [4], antimicrobial [5], anti-inflammatory [4], immunomodulatory [6] and anticancer activities [5]. Microalgae are found in both marine and terrestrial habitats due to their ability to adapt and survive in very different environments. ...
Simple Summary
Microalgae are a huge renewable and eco-friendly source of natural compounds, including vitamins, carbohydrates, pigments, sterols and lipids. They have found applications in different industrial sectors, including the pharmaceutical, nutraceutical and cosmeceutical fields. Isochrysis galbana, a marine flagellate belonging to the Haptophyta phylum, thanks to its nutraceutical composition has been proposed as a shellfish diet (Shellfish Diet 1800®) as well as in the composition of cookies, fresh pasta and yogurt. I. galbana powder, extracts or pure molecules have shown interesting bioactivities, such as antioxidant, antidiabetes and antituberculosis, while the antiproliferative activity is mainly related to lung lymphoblasts. In the current study, we aimed to identify metabolic pathways activated in stressful conditions (stationary growth phase) by transcriptomic and bioactivity-guided fractionation. Overall, the results showed antiproliferative activities against melanoma cells, suggesting new possible applications in cancer prevention and treatment.
Abstract
Haptophytes are important primary producers in the oceans, and among the phylum Haptophyta, the flagellate Isochrysis galbana has been found to be rich in high-value compounds, such as lipids, carotenoids and highly branched polysaccharides. In the present work, I. galbana was cultured and collected at both stationary and exponential growth phases. A transcriptomic approach was used to analyze the possible activation of metabolic pathways responsible for bioactive compound synthesis at the gene level. Differential expression analysis of samples collected at the exponential versus stationary growth phase allowed the identification of genes involved in the glycerophospholipid metabolic process, the sterol biosynthetic process, ADP-ribose diphosphatase activity and others. I. galbana raw extracts and fractions were tested on specific human cancer cells for possible antiproliferative activity. The most active fractions, without affecting normal cells, were fractions enriched in nucleosides (fraction B) and triglycerides (fraction E) for algae collected in the exponential growth phase and fraction E for stationary phase samples. Overall, transcriptomic and bioactivity data confirmed the activation of metabolic pathways involved in the synthesis of bioactive compounds giving new insights on possible Isochrysis applications in the anticancer sector.
... The first compound used for drug production was cytarabine (marketed name, Cytosar-U ® ) that derived from Caribbean marine sponge, spongian nucleoside, in 1959 and approved for cancer in 1969, and then vidarabine approved in 1979 as antiviral (Martins et al. 2014). In totally, eight natural product-derived drugs have been approved by Food and Drug Administration (FDA) and/or the European Medical Agency (EMA) that the origin of two drugs is marine peptides (Jaspars et al. 2016;Jimenez et al. 2020). In recent years, increased desire to study biological and pharmaceutical properties of peptides has been observed, so that over 60 peptides are as market drug and many peptides are in clinical pipeline, too (Arumugam et al. 2019). ...
Marine organisms contain valuable chemical compounds as secondary metabolites such as bioactive peptides that survive in harsh marine environments produced by organisms. They have been considered by scientists for use in medicine and pharmaceutical researches due to their unique and unknown biological properties. Studies on a variety of marine-derived peptides have shown that these compounds as antimicrobial, antiviral, antioxidant, antihypertensive, and anticancer agents can be useful in the treatment of various diseases. While many marine peptides are in various phases of clinical trials, two marine peptide-derived drugs have been approved by the Food and Drug Administration (FDA), too. This chapter highlights the recent two decades of researches on the biological properties of peptides derived from a variety of living organisms, including microbes, plants, and marine animals, in vivo, vitro, and clinical trials and their potential for disease treatment.
Research on marine bioactive compounds has increased significantly. These marine natural products have industrial, biotechnological, and pharmaceutical applications. Venomous cnidarians are a fundamental source of bioactive molecules. Millepora “fire coral” species (Phylum cnidaria) are the second most copious coral reef-forming and possess sticking toxic properties. Millepora hydrocorals sting can inflict a painful local reaction and systemic effects in humans. Here, we present the state of the art for the principal biological activities identified from these venomous organisms with classical and modern approaches. This study also includes a review of the general features of organisms of the genus Millepora, the existing toxinological reports, and the prospects for hydrocoral research. We aim to openly share information on Millepora toxin expertise to enable the invention of novel drugs and biotechnological and research tools.
Marine diatom Chaetoceros gracilis have been known as the key player regulating the nutritional content of aquaculture species. Being able to synthesize an array of high value bioactive compounds like amino acids, lipids, terpenoids and polysaccharides, it also serves as potential therapeutic and nutraceutical agent. Thus, this in silico-based study elucidates the interactive association of different compounds, proteins and pathways of the diatom C. gracilis through an integrated network pharmacology and molecular docking approach. According to the Network analysis of the 41 compounds detected, saturated hydrocarbons, diterpenoids and phenolic compounds scored the highest degree (score >140). These compounds further coded for approximately 349 protein targets and almost 490 different pathways. HSP90AA1, STAT3, HIF1A, MTOR, ESR1, PIK3CA, MAPK1 and PTGS2 secured highest degree of protein-protein interaction according to STRING database. The gene enrichment analysis further revealed that these proteins were closely associated with metabolic pathways like Pathways in cancer, neuroactive ligand-receptor interaction, calcium and cAMP signaling pathway, PI3K-Akt signaling pathway, Alzheimer disease and pathways of neurodegeneration which played an instrumental role in the metabolism of diseases and disorders like cancers of breast, prostrate, and liver, schizophrenia and other mental and hypertensive disorders. Following which, molecular docking and toxicity assessment of a few novel compounds was done with mTOR and HSP90AA1 which revealed promising and stable interactions. Thus, this study provides the first in silico insight outlining the anti-cancerous and neuroprotective potential of novel bioactive compounds derived from marine diatom C.gracilis.
Many biologically active compounds found in micro and macroalgae have multiple therapeutic capabilities, such as antibacterial as well as antifungal properties. Besides that, it has antiviral and antioxidative actions. As a result, there are several possibilities to produce pharmaceutical products for human well-being from algal sources. Pharmaceutical industries use algal biomass as the cell wall of algae is composed of different carbohydrates. The fatty acids present in algal biomass make it a preferred biologically active substance that is immensely beneficial to the pharmaceutical sector. Compared to other biofuel products such as biodiesel, algal biomass is more energetically favourable since it can be used in the wet state without any requirement of further drying techniques, thus making it cost-efficient. This chapter describes the importance of pharmaceutical products derived from algal biomass and their impact on the growth of the pharmaceutical industry.
Marine genetic resources hold great value for biotechnological innovation and sustainability-oriented research. However, studies indicate that intellectual property rights pertaining to these resources are concentrated in a handful of companies and countries, triggering contentious international debates. This paper highlights an overlooked dimension: scientists and their affiliated countries as central actors in the provision of marine genetic research. We introduce a dataset of 23,417 marine genetic studies and trace patent references to these studies. Our analysis reveals that molecular biological research, oftentimes on bacterial species, attracts the most patenting interest. Some countries own relatively more patents than they provide in science, with the U.S. benefiting the most from available research. Science by G77 researchers has seen limited uptake in patents. These findings aim to inform international biodiversity regimes, such as the UN treaty on Biodiversity Beyond National Jurisdiction (BBNJ), on how to more equitably distribute marine genetic resources’ economic, socio-cultural, and ecological benefits.
INTRODUCTION. Nowadays the issues concerning conservation of marine biological diversity become important for the community of States in the light of the expansion of the scale of economic activity in marine spaces and of the opportunities of using such resources. At the universal contractual level an answer was proposed to a number of questions that have arisen in this area: on March 4, 2023, the text of the Agreement (under the 1982 United Nations Convention on the Law of the Sea) with a long title: “on the Conservation and Sustainable Use of Marine Biological Diversity of Areas Beyond National Jurisdiction” was finalized. It is predicted that the entry into force of this Agreement in the future will create a multilateral legal basis for conservation of biological diversity on the high seas, with the orderly use of its biological resources, to protect such diversity based on the principle of cooperation between States.
The purpose of the article is to analyze the legal regime of marine genetic resources conservation based on the text of this Agreement.
MATERIALS AND METHODS. The subject of this study comprises international treaties, international customs, general principles of international law and other sources of international law related to conservation of marine biodiversity in general. The methodological basis of the research is represented by a wide range of research methods, namely: formal-legal, comparative-legal, historical-legal and system-structural methods. In addition, the author applied the methods of analysis and generalization.
RESEARCH RESULTS. The article presents a comprehensive analysis of the international legal regime of marine genetic resources based on the provisions of the Agreement under the United Nations Convention on the Law of the Sea on the conservation and sustainable use of marine biological diversity of areas beyond national jurisdiction. The author considers the history of the development of the draſt Agreement, analyzes its main provisions, and pays special attention to its innovative legal mechanisms.
The author proposes their assessment of the content of the draſt Agreement as a universal legal basis for the conservation of marine biological diversity, and suggests some options for strengthening international cooperation in this area.
DISCUSSION AND CONCLUSIONS. As a result of the study, it can be stated that the draſt Agreement, prepared over many years of negotiations and published in March 2023, is a significant political and legal achievement of a universal level in the field of marine biodiversity conservation. At the same time, one can not fail to note the rather general nature of this document, as well as the fact that the entry into force of the Agreement may also require considerable time: objectively, the interests of developed and developing countries in this area are not always close; moreover, each State party to the Agreement accepts the obligation, among other things, that the use of marine natural resources should be linked to the obligation to protect marine environment, and this is always sensitive: a number of developed countries, as is known, under the pretext of economic concern, impose on developing States “green” products of their enterprises, which exacerbates the gap between developed and developing States.
That is why the author comes to the conclusion that the international community, along with the development of a universal international treaty, could take the path of developing regional agreements to clarify such a legal regime, which would also contribute to the strengthening of the legal regime for biodiversity conservation at the universal level.
Influenza is a contagious viral infection of the respiratory tract, affecting nearly 10% of the world's population, each year. The aim of this study was to extract and identify antiviral compounds against the influenza-A virus (H1N1) from different species of Egyptian marine algae. Three samples of marine macroalgae species were extracted and the antiviral activity of the extracts were tested on Madin Darby Canine Kidney cells. The bioactive compounds present in the most active fractions were identified using gas chromatography-mass spectrometry (GC-MS), then the binding potentials of the identified compounds were examined towards neuraminidase (NA) of the influenza-A virus using molecular docking. The methanolic extract of Sargassum aquifolium showed promising in-vitro antiviral activity with a selectivity index (SI) value of 101. The GC-MS analysis showed twelve compounds and the molecular docking analysis found that tetradecanoic acid showed the strongest binding affinities towards the NA enzyme.
Fungi are the most diverse living organisms on planet Earth, where their ubiquitous presence in various ecosystems offers vast potential for the research and discovery of new, naturally occurring medicinal products. Concerning human health, cancer remains one of the leading causes of mortality. While extensive research is being conducted on treatments and their efficacy in various stages of cancer, finding cytotoxic drugs that target tumor cells with no/less toxicity toward normal tissue is a significant challenge. In addition, traditional cancer treatments continue to suffer from chemical resistance. Fortunately, the cytotoxic properties of several natural products derived from various microorganisms, including fungi, are now well-established. The current review aims to extract and consolidate the findings of various scientific studies that identified fungi-derived bioactive metabolites with antitumor (anticancer) properties. The antitumor secondary metabolites identified from extremophilic and extremotolerant fungi are grouped according to their biological activity and type. It became evident that the significance of these compounds, with their medicinal properties and their potential application in cancer treatment, is tremendous. Furthermore, the utilization of omics tools, analysis, and genome mining technology to identify the novel metabolites for targeted treatments is discussed. Through this review, we tried to accentuate the invaluable importance of fungi grown in extreme environments and the necessity of innovative research in discovering naturally occurring bioactive compounds for the development of novel cancer treatments.
Diabetes mellitus (DM) is a chronic metabolic disorder recognized as a major health problem globally. A defective insulin activity contributes to the prevalence and expansion of DM. Treatment of DM is often hampered by limited options of conventional therapies and adverse effects associated with existing procedures. This has led to a spike in the exploration for potential therapeutic agents from various natural resources for clinical applications. The marine environment is a huge store of unexplored diversity of chemicals produced by a multitude of organisms. To date, marine microorganisms, microalgae, macroalgae, corals, sponges, and fishes have been evaluated for their anti-diabetic properties. The structural diversity of bioactive metabolites discovered has shown promising hypoglycaemic potential through in vitro and in vivo screenings via various mechanisms of action, such as PTP1B, α-glucosidase, α-amylase, β-glucosidase, and aldose reductase inhibition as well as PPAR alpha/gamma dual agonists activities. On the other hand, hypoglycaemic effect is also shown to be exerted through the balance of antioxidants and free radicals. This review highlights marine-derived chemicals with hypoglycaemic effects and their respective mechanisms of action in the management of DM in humans.
Fungi are the second largest group of living organisms that exist as distinct achlorophyllous, filamentous hyphae growing in diverse habitats depending upon their nutrition source(s). The nutrition sources may alter the growth and fungal secondary metabolite (SM) production. Fungi are an outstanding source of bioactive metabolites used in food and agriculture industry and therapeutics. The innumerable SMs produced from fungi play a vital role as anticancer, antibacterial, antifungal, antioxidant, anti-inflammatory and antidiabetic agents. For instance, the food and drug administration (FDA) has approved fungal drugs like penicillin, cephalosporin, cyclosporine A and lovastatin for commercial use. In addition, fungi have the potential to produce plant-derived SMs such as taxol, vinblastine, vincristine, podophyllotoxin and camptothecin. All the fungal SMs are characterized by techniques like fungal cultivation, extraction, purification and structural characterization using chromatographic and spectroscopic analysis. Exploring the SMs of fungi from rare or specific niches may result in the discovery of novel compounds. Each new fungus has the capacity for producing as yet unexplored compounds with bioactivities that can be altered for therapeutic uses. Such potential fungal SMs can be developed to address existing challenges in the medical field. This chapter focuses on different types of fungi used as medicines for the treatment of various human diseases.KeywordsFungiSecondary metabolitesBioactive compoundsFungal drugsTherapeutic value
The article examines whether the legal regime of genetic resources is outlined in the context of applicable rules relating to biological diversity. The purpose of the research is to confute the prospects for the formation of a universal legal regime for genetic resources, in the context of the draft UN Agreement on the Conservation and Sustainable Use of Marine Biological Diversity in Areas beyond National Jurisdiction, and the possibilities of using regional mechanisms in this domain.
The methodology of the research includes the formal legal, comparative, historical, systemic and structural methods. The authors analyze and examine applicable international legal sources, including the 1992 Convention on Biological Diversity and its 2010 Nagoya Protocol. On the basis of the systemic and structural method the authors carry out the analysis of the sources of international law related to the conservation and sustainable use of genetic and other biological resources.
The main results. The international community’s interest in genetic resources results from the growing need to take more informed environmental decisions. The relevant universal legal basis, created by the 1992 Convention on Biological Diversity, does not provide answers to some important questions, including the detailed legal definition of the term “genetic resources”, though the relevant definition contained in the 1992 Convention remains the only one that has been accepted by a large number of states. It is possible that states will be able to develop a more concrete legal rules relating to the genetic resources in the course of negotiating the UN Agreement on the Conservation and Sustainable Use of Marine Biological Diversity in Areas beyond National Jurisdiction. However, the development of such a universal international treaty might require a lot of effort in order to reconcile the divergent interests of states.
Conclusions. Based on the analysis of applicable international law, the authors assert that the generally outlined legal basis for conservation of biodiversity, laid down by the 1992 Convention, demands further detailing in the modern context. The UN process on the conservation and sustainable use of marine biological diversity in areas beyond national jurisdiction is likely to take considerable efforts of participating actors before the appropriate legal mechanisms are agreed upon. So regional legal regimes might be an appropriate way to ensure the efficient management of genetic resources taking into account peculiarities of each individual region.
Seas and oceans have been explored for the last 70 years in search of new compounds that can support the battle against cancer. Marine polysaccharides can act as nanomaterials for medical applications and marine-derived bioactive compounds can be applied for the biosynthesis of metallic and nonmetallic nanoparticles. Nanooncology can be used in numerous fields including diagnostics, serving as drug carriers or acting as drugs. This review focuses on marine-derived nanoparticles with potential oncological applications. It classifies organisms used for nanoparticle production, explains the production process, presents different types of nanoparticles with prospective applications in oncology, describes the molecular pathways responsible for numerous nanomedicine applications, tags areas of nanoparticle implementation in oncology and speculates about future directions.
The marine ecosystem contains a solution for food, shelter, pharmaceutical problems and has a key role in the economy of the country as tourism. The Gulf of Kachchh, known for its high tides and the coral reefs are less explored for its antibiotic activity due to the coral bleaching and diseases. The bacterial strains in the coral Porites lutea are determined to possess antibiotic activity against bacterial strains such as E.coli, P. aeruginosa, S. aureus and S. faecalis. Among thirty bacterial strains isolated from the tissue, skeleton and mucus, two bacterial strains resulted in the better antagonistic activity. The antibiotic compound extracted from both the bacteria elucidated to be 4-[(2E)-4-hydroxypent-2-en-1-yl]-5,6-dihydro-2H-pyran-2-one. Further, through ADMET prediction it was inferred that it is an effective drug lead as it reports less toxicity and better drug-likeliness. The study also includes the effect of Poly Hydroxy Butarate (PHB) production by the isolated bacterial strain.
The sea is a vast ecosystem that has remained primarily unexploited and untapped, resulting in numerous organisms. Consequently, marine organisms have piqued the interest of scientists as an abundant source of natural resources with unique structural features and fascinating biological activities. Marine macrolide is a top-class natural product with a heavily oxygenated polyene backbone containing macrocyclic lactone. In the last few decades, significant efforts have been made to isolate and characterize macrolides' chemical and biological properties. Numerous macrolides are extracted from different marine organisms such as marine microorganisms, sponges, zooplankton, molluscs, cnidarians, red algae, tunicates, and bryozoans. Notably, the prominent macrolide sources are fungi, dinoflagellates, and sponges. Marine macrolides have several bioactive characteristics such as antimicrobial (antibacterial, antifungal, antimalarial, antiviral), anti-inflammatory, antidiabetic, cytotoxic, and neuroprotective activities. In brief, marine organisms are plentiful in naturally occurring macrolides, which can become the source of efficient and effective therapeutics for many diseases. This current review summarizes these exciting and promising novel marine macrolides in biological activities and possible therapeutic applications.
Marine organisms have developed physiological and biochemical strategies to survive under the exposure of UV-B radiation. In particular, Antarctic marine bacteria, exposed to extremes of temperature, UV and ice, have adapted to cope with UV radiation by producing photoprotective molecules. Here, we describe (1) the sampling strategy to collect marine samples (surface water/ice and sediment samples) and (2) the selection strategy to isolate in these samples only UV-resistant marine bacteria.Key wordsUV radiationUV-C assayMarine bacteriumPhotoprotectionBioactive compoundIsolation strategy
The marine environment offers an extensive source of secondary metabolites with promising biological activities to start drug discovery processes. Marine polyketides are a class of compounds with diverse and interesting biological properties. Their biosynthetic production mechanism of versatile assembly confers these compounds remarkable diversity both in terms of structural complexity and biological activity. This review focuses on marine aliphatic polyketides or mixed non-ribosomal peptide-polyketide compounds in advanced drug discovery stages. The isolation, drug development process, supply sources and clinical status of these polyketide or mixed peptide-polyketide compounds, as well as their potential as drug candidates, is hereby described.
This review covers the literature published in 2013 for marine natural products (MNPs), with 982
citations (644 for the period January to December 2013) referring to compounds isolated from
marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians,
bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and
microorganisms. The emphasis is on new compounds (1163 for 2013), together with the relevant
biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first
syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been
included.
The first marine natural products that served as leads or scaffolds for medicines were discovered in the middle of last century: the arabinosyl glycosides from the marine sponge Tectitethya crypta. Synthesis and modifications of the natural molecules generated antiviral and antileukemic drugs developed in the 1970’s and in the following decades, including the first effective treatment against HIV infection.
With the improvement of techniques for the elucidation of chemical structure of the molecules, as well for chemical synthesis, especially from the 1990’s, there was an increase in the number of bioactive natural products characterized from marine organisms. New chemical structures with high specificity towards molecular targets in cells allowed the development of new drugs with indication for the treatment of several illnesses, from cancer to new antibiotics, and even neurological disorders.
Currently there are at least 13 molecules derived from marine natural products on advanced clinical trials, and nine were approved to be used as medicines. Considering that in the past eight years, more than 1,000 new compounds from marine organisms were described, per year, the expectation is that many more drugs will be derived from marine natural products in a near future.
Nowadays the global tendency towards physical activity reduction and an augmented dietary intake of fats, sugars and calories is leading to a growing propagation of overweight, obesity and lifestyle-related diseases, such diabetes, hypertension, dyslipidemia and metabolic syndrome. In particular, obesity, characterized as a state of low-level inflammation, is a powerful determinant both in the development of insulin resistance and in the progression to type 2 diabetes. A few molecular targets offer hope for anti-obesity therapeutics. One of the keys to success could be the induction of uncoupling protein 1 (UCP1) in abdominal white adipose tissue (WAT) and the regulation of cytokine secretions from both abdominal adipose cells and macrophage cells infiltrated into adipose tissue. Anti-obesity effects of fucoxanthin, a characteristic carotenoid, exactly belonging to xanthophylls, have been reported. Nutrigenomic studies reveal that fucoxanthin induces UCP1 in abdominal WAT mitochondria, leading to the oxidation of fatty acids and heat production in WAT. Fucoxanthin improves insulin resistance and decreases blood glucose levels through the regulation of cytokine secretions from WAT. The key structure of anti-obesity effect is suggested to be the carotenoid end of the polyene chromophore, which contains an allenic bond and two hydroxyl groups. Fucoxanthin, which can be isolated from edible brown seaweeds, recently displayed its many physiological functions and biological properties. We reviewed recent studies and this article aims to explain essential background of fucoxanthin, focusing on its promising potential anti-obesity effects. In this respect, fucoxanthin can be developed into promising marine drugs and nutritional products, in order to become a helpful functional food.
The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories.
A bioassay guided fractionation of the ethyl acetate extract from culture broths of the strain Streptomyces zhaozhouensis CA-185989 led to the isolation of three new polycyclic tetramic acid macrolactams (1–3) and four known compounds. All the new compounds were structurally related to the known Streptomyces metabolite ikarugamycin (4). Their structural elucidation was accomplished using a combination of electrospray-time of flight mass spectrometry (ESI-TOF MS) and 1D and 2D NMR analyses. Compounds 1–3 showed antifungal activity against Aspergillus fumigatus, Candida albicans and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).
As long ago as the sixteenth century, Paracelsus recognized that 'the dose makes the poison'. Indeed, environmental concentrations of pharmaceuticals excreted by humans are limited, most importantly because a defined dose is given to just a fraction of the population. By contrast, recent studies have identified direct emission from drug manufacturing as a source of much higher environmental discharges that, in some cases, greatly exceed toxic threshold concentrations. Because production is concentrated in specific locations, the risks are not linked to usage patterns. Furthermore, as the drugs are not consumed, metabolism in the human body does not reduce concentrations. The environmental risks associated with manufacturing therefore comprise a different, wider set of pharmaceuticals compared with those associated with risks from excretion. Although pollution from manufacturing is less widespread, discharges that promote the development of drug-resistant microorganisms can still have global consequences. Risk management also differs between production and excretion in terms of accountability, incentive creation, legal opportunities, substitution possibilities and costs. Herein, I review studies about industrial emissions of pharmaceuticals and the effects associated with exposure to such effluents. I contrast environmental pollution due to manufacturing with that due to excretion in terms of their risks and management and highlight some recent initiatives.
Marine microorganisms continue to be a source of structurally and biologically novel compounds with potential use in the biotechnology industry. The unique physiochemical properties of the marine environment (such as pH, pressure, temperature, osmolarity) and uncommon functional groups (such as isonitrile, dichloroimine, isocyanate, and halogenated functional groups) are frequently found in marine metabolites. These facts have resulted in the production of bioactive substances with different properties than those found in terrestrial habitats. In fact, the marine environment contains a relatively untapped reservoir of bioactivity. Recent advances in genomics, metagenomics, proteomics, combinatorial biosynthesis, synthetic biology, screening methods, expression systems, bioinformatics, and the ever increasing availability of sequenced genomes provides us with more opportunities than ever in the discovery of novel bioactive compounds and biocatalysts. The combination of these advanced techniques with traditional techniques, together with the use of dereplication strategies to eliminate known compounds, provides a powerful tool in the discovery of novel marine bioactive compounds. This review outlines and discusses the emerging strategies for the biodiscovery of these bioactive compounds.
With the adoption of the Nagoya Protocol in 2010, an additional legal instrument under the Convention on Biological Diversity (1992), the legal landscape surrounding the access to and utilization of genetic resources will change. This is likely to impact working procedures for scientists, turning pre-existing ethics into legal obligations. The aim of this article is to inform scientists on the global access and benefit-sharing framework which has been set by the Convention on Biological Diversity and its Nagoya Protocol, focusing specifically on their application to marine genetic resources for which the United Nations Convention on the Law of the Sea (1982) also has relevance.
The marine environment harbors a number of macro and micro organisms that have developed unique metabolic abilities to ensure their survival in diverse and hostile habitats, resulting in the biosynthesis of an array of secondary metabolites with specific activities. Several of these metabolites are high-value commercial products for the pharmaceutical and cosmeceutical industries. The aim of this review is to outline the paths of marine natural products discovery and development, with a special focus on the compounds that successfully reached the market and particularly looking at the approaches tackled by the pharmaceutical and cosmetic companies that succeeded in marketing those products. The main challenges faced during marine bioactives discovery and development programs were analyzed and grouped in three categories: biodiversity (accessibility to marine resources and efficient screening), supply and technical (sustainable production of the bioactives and knowledge of the mechanism of action) and market (processes, costs, partnerships and marketing). Tips to surpass these challenges are given in order to improve the market entry success rates of highly promising marine bioactives in the current pipelines, highlighting what can be learned from the successful and unsuccessful stories that can be applied to novel and/or ongoing marine natural products discovery and development programs.
Carotenoids constitute a ubiquitous group of isoprenoid pigments. They are very efficient physical quenchers of singlet oxygen and scavengers of other reactive oxygen species. Carotenoids can also act as chemical quenchers undergoing irreversible oxygenation. The molecular mechanisms underlying these reactions are still not fully understood, especially in the context of the anti- and pro-oxidant activity of carotenoids, which, although not synthesized by humans and animals, are also present in their blood and tissues, contributing to a number of biochemical processes. The antioxidant potential of carotenoids is of particular significance to human health, due to the fact that losing antioxidant-reactive oxygen species balance results in "oxidative stress", a critical factor of the pathogenic processes of various chronic disorders. Data coming from epidemiological studies and clinical trials strongly support the observation that adequate carotenoid supplementation may significantly reduce the risk of several disorders mediated by reactive oxygen species. Here, we would like to highlight the beneficial (protective) effects of dietary carotenoid intake in exemplary widespread modern civilization diseases, i.e., cancer, cardiovascular or photosensitivity disorders, in the context of carotenoids' unique antioxidative properties.
The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743), Eribulin (a synthetic derivative based on the structure of halichondrin B), and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin) as a warhead, have been approved for use in humans (Adcetris®). In this review, we show the compounds derived from marine sources that are currently in clinical trials against cancer. We have included brief discussions of the approved agents, where they are in trials to extend their initial approved activity (a common practice once an agent is approved), and have also included an extensive discussion of the use of auristatin derivatives as warheads, plus an area that has rarely been covered, the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies.
Although metastatic breast cancer remains essentially incurable, many patients previously treated with an anthracycline, taxane, and capecitabine are relatively fit and keen to receive further therapy. Several drugs are used in this setting, but with little evidence of clinically relevant benefit, and none have previously shown improved survival. Eribulin (Halaven®) is a nontaxane tubulin-binding agent with a novel mode of action, and was recently approved by the European Medicines Agency and US Food and Drug Agency as a single agent for patients with heavily pretreated metastatic breast cancer. This review provides an overview of the discovery, and preclinical and clinical development of eribulin, culminating in the recently published EMBRACE metastatic breast cancer study.
Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed.
The chemical investigation of the recently described Mediterranean Homoscleromorpha sponge Oscarella balibaloi revealed an original family of five closely related glucosylated sesterterpenes 1–4, named balibalosides. Their structure elucidation was mainly inferred from NMR and HRMS data analyses. Balibalosides differ by the pattern of acetyl substitutions on the three sugar residues linked to the same aglycone sesterterpenoid core. From a biosynthetic perspective, these compounds may represent intermediates in the pathways leading to more complex sesterterpenes frequently found in Dictyoceratida, a sponge Order belonging to Demospongiae, a clade which is phylogenetically distinct from the Homoscleromorpha. While steroid and triterpenoid saponins were already well known from marine sponges, balibalosides are the first examples of glycosilated sesterterpenes.
The proteasome has emerged as an important clinically relevant target for the treatment of hematologic malignancies. Since the Food and Drug Administration approved the first-in-class proteasome inhibitor bortezomib (Velcade® ) for the treatment of relapsed/refractory multiple myeloma (MM) and mantle cell lymphoma, it has become clear that new inhibitors are needed that have a better therapeutic ratio, can overcome inherent and acquired bortezomib resistance and exhibit broader anti-cancer activities. Marizomib (NPI-0052; salinosporamide A) is a structurally and pharmacologically unique β-lactone-γ-lactam proteasome inhibitor that may fulfill these unmet needs. The potent and sustained inhibition of all three proteolytic activities of the proteasome by marizomib has inspired extensive preclinical evaluation in a variety of hematologic and solid tumor models, where it is efficacious as a single agent and in combination with biologics, chemotherapeutics and targeted therapeutic agents. Specifically, marizomib has been evaluated in models for multiple myeloma, mantle cell lymphoma, Waldenstrom's macroglobulinemia, chronic and acute lymphocytic leukemia, as well as glioma, colorectal and pancreatic cancer models, and has exhibited synergistic activities in tumor models in combination with bortezomib, the immunomodulatory agent lenalidomide (Revlimid® ), and various histone deacetylase inhibitors. These and other studies provided the framework for ongoing clinical trials in patients with MM, lymphomas, leukemias and solid tumors, including those who have failed bortezomib treatment, as well as in patients with diagnoses where other proteasome inhibitors have not demonstrated significant efficacy. This review captures the remarkable translational studies and contributions from many collaborators that have advanced marizomib from seabed to bench to bedside.
Covering: 2010. Previous review: Nat. Prod. Rep., 2011, 28, 196. This review covers the literature published in 2010 for marine natural products, with 895 citations (590 for the period January to December 2010) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1003 for 2010), together with the relevant biological activities, source organisms and country of origin. Biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.
Brentuximab vedotin (SGN-35) is an antibody-drug conjugate (ADC) directed against the CD30 antigen expressed on Hodgkin lymphoma and anaplastic large cell lymphoma. SGN-35 consists of the cAC10 chimerized IgG1 monoclonal antibody SGN30, modified by the addition of a valine-citrulline dipeptide linker to permit attachment of the potent inhibitor of microtubule polymerization monomethylauristatin E (MMAE). In phase II trials, SGN-35 produced response rates of 75% in patients with Hodgkin lymphoma (n = 102) and 87% in patients with anaplastic large cell lymphoma (n = 30). Responses to SGN-35 might be related not only to the cytotoxic effect due to release of MMAE within the malignant cell but also to other effects. First, SGN-35 may signal malignant cells through CD30 ligation to deliver an apoptotic or proliferative response. The former would amplify the cytotoxicity of MMAE. A proliferative signal delivered in the context of MMAE intoxication could enhance cell death. Second, the efficacy of SGN-35, particularly in Hodgkin lymphoma, might be attributed to its effect on the tumor microenvironment. Diffusion of free MMAE from the targeted tumor cells could result in a bystander effect that kills the normal supporting cells in close proximity to the malignant cells. The elimination of T regulatory cells that inhibit cytotoxic effector cells and elimination of cells that provide growth factor support for Hodgkin/Reed–Sternberg cells could further enhance the cytotoxic activity of SGN-35. Here we review the biology of SGN-35 and the clinical effects of SGN-35 administration. Clin Cancer Res; 17(20); 6428–36. ©2011 AACR.
The diversity of life is one of the most striking aspects of our planet; hence knowing how many species inhabit Earth is among the most fundamental questions in science. Yet the answer to this question remains enigmatic, as efforts to sample the world's biodiversity to date have been limited and thus have precluded direct quantification of global species richness, and because indirect estimates rely on assumptions that have proven highly controversial. Here we show that the higher taxonomic classification of species (i.e., the assignment of species to phylum, class, order, family, and genus) follows a consistent and predictable pattern from which the total number of species in a taxonomic group can be estimated. This approach was validated against well-known taxa, and when applied to all domains of life, it predicts ~8.7 million (± 1.3 million SE) eukaryotic species globally, of which ~2.2 million (± 0.18 million SE) are marine. In spite of 250 years of taxonomic classification and over 1.2 million species already catalogued in a central database, our results suggest that some 86% of existing species on Earth and 91% of species in the ocean still await description. Renewed interest in further exploration and taxonomy is required if this significant gap in our knowledge of life on Earth is to be closed.
Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed.
Recent advances in genomics and genome sequencing technologies provide a wealth of DNA sequence data that sheds new light on the causes of epilepsy. Animal models help to elucidate the biological significance of such disease-associated DNA sequence variation by enabling functional relationships between disease genotypes and phenotypes to be defined. Here I review the unique combination of attributes that is allowing the zebrafish to play increasingly prominent roles in investigating the mechanisms underlying epilepsy and in discovering new drugs to treat this condition. New techniques for genome editing now allow the zebrafish genome to be engineered to recapitulate key elements of the patterns of genomic variation that are observed in epilepsy patients. Moreover, a sophisticated range of imaging technologies enables spatio-temporal patterns of neural activity to be visualised in the intact zebrafish nervous system with single-cell levels of resolution. These technologies, together with refined techniques tor electrophysiological analysis and non-invasive modulation of specific neuronal circuit functions, allow the impacts of defined genetic variation on in vivo patterns of neural activity to be analysed in unprecedented depth. The pharmacological tractability of the zebrafish, and the amenability of its embryonic and larval stages to high throughput phenotype analysis, are also enabling advances in anti-epileptic drug discovery. Combining such pharmacological screening approaches with new tools for genome editing, live imaging, electrophysiology, conditional manipulation of circuit activity and behavioural analysis of zebrafish, could facilitate step changes in both understanding of epileptogenesis and in vivo discovery of new and improved anti-epileptic drugs.
Copyright © 2015. Published by Elsevier B.V.
Journal of Antibiotics, official journal of the Japan Antibiotics Research Association, is a print and online publication that focuses on research on antibiotics and related types of medicinal substances
Conopeptides are the peptidic components of the venoms of marine cone snails from the Conus genus. Aside from their natural function in pharmacologically immobilizing prey, they have attracted the attention of drug designers in recent years because of their potency and selectivity at a range of pharmaceutically important targets in mammals, including ion channels and neurotransmitter transporters. One conopeptide, MVIIA (ziconotide, Prialt®), is on the market for the treatment of intractable neuropathic pain and others are in preclinical or clinical development. This article provides an overview of recent developments in the conopeptide field, with particular reference to their potential applications as drugs for the treatment of pain. Copyright © 2011 Prous Science, S.A.U. or its licensors. All rights reserved.
New antitumor polyether macrolides were successfully isolated from a marine sponge, Halichondria okadai Kadota. One of them, halichondrin B exhibited remarkable in vivo antitumor activity. Physiological properties and structures of these compounds are reported. The structures have been characterized by a long-straight carbon chain, a polyether macrolide, and a novel 2,6,9-trioxatricyclo left bracket 3. 3. 2. 0**3,**7 right bracket decane system which is the first example in natural products.
Drug discovery methods often rely on in vitro assays to identify compounds with specific types of biochemical activity, but predicting how a psychoactive drug will affect behavior requires direct testing of candidate compounds in animal models. Rihel et al. devised a high-throughput screen to identify compounds that affect rest-wake activity in zebrafish larvae and quantify the behavioral effects. They sorted the compounds into clusters based on their “behavioral fingerprint,” a set of behavioral changes elicited by each compound. Analysis of the data revealed that compounds that elicit similar behavioral changes often affect the same molecular targets or pathways, and compounds of similar structure produced similar behavioral effects in vivo. The authors were able to use the data set to predict the biological targets of uncharacterized compounds based on those of well-characterized compounds with which they cluster in the behavioral fingerprint analysis. The screen demonstrated that many aspects of neuropharmacology are conserved between mammals and zebrafish, so this model might also be useful for biochemically characterizing the regulation and pharmacology of complex behaviors. The results also suggested additional pathways that might be involved in modulating rest-wake activities. For example, several anti-inflammatory compounds increased wakeful activity during the day but not at night, suggesting that anti-inflammatory signaling pathways not only increase sleep in response to infection but also modulate daytime activity under normal conditions. These findings might enable researchers to predict biological targets or behavioral effects of novel compounds based on structural or biochemical aspects shared with well-characterized drugs, and they may also inform rational drug design.
Licensed to kill: A new antibiotic, anthracimycin, produced by a marine-derived actinomycete in saline culture, shows significant activity toward Bacillus anthracis, the bacterial pathogen responsible for anthrax infections. Chlorination of anthracimycin gives a dichloro derivative that retains activity against Gram-positive bacteria, like anthrax, but also shows activity against selected Gram-negative bacteria.
The declining trends in microbial metabolite and natural products research and the refocusing of this research area are discussed. Renewing natural products research requires inexhaustible natural resources, as well as new genetic techniques and microbial sources, including endophytic microbes. The numbers of known bioactive metabolites are summarized according to their microbiological origin, biological activities and chemical structures. Synthetic and natural product-based libraries are also compared. Importantly, the wide range of microbial metabolite bioactivities, future trends and the importance of prioritizing natural products over synthetic compounds are emphasized.
The global marine pharmaceutical pipeline consists of three Food and Drug Administration (FDA) approved drugs, one EU registered drug, 13 natural products (or derivatives thereof) in different phases of the clinical pipeline and a large number of marine chemicals in the preclinical pipeline. In the United States there are three FDA approved marine-derived drugs, namely cytarabine (Cytosar-U®, Depocyt®), vidarabine (Vira-A®) and ziconotide (Prialt®). The current clinical pipeline includes 13 marine-derived compounds that are either in Phase I, Phase II or Phase III clinical trials. Several key Phase III studies are ongoing and there are seven marine-derived compounds now in Phase II trials. The preclinical pipeline continues to supply several hundred novel marine compounds every year and those continue to feed the clinical pipeline with potentially valuable compounds. From a global perspective the marine pharmaceutical pipeline remains very active, and now has sufficient momentum to deliver several additional compounds to the marketplace in the near future; this review provides a current view of the pipeline.
Marine life forms are an important source of structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. These success stories have had to overcome difficulties inherent to natural products-derived drugs, such as adequate sourcing of the agent and issues related to structural complexity. Nevertheless, several marine-derived agents are now approved, most as "first-in-class" drugs, with five of seven appearing in the past few years. Additionally, there is a rich pipeline of clinical and preclinical marine compounds to suggest their continued application in human medicine. Understanding of how these agents are biosynthetically assembled has accelerated in recent years, especially through interdisciplinary approaches, and innovative manipulations and re-engineering of some of these gene clusters are yielding novel agents of enhanced pharmaceutical properties compared with the natural product.
Patients with advanced or metastatic non-gastrointestinal stromal tumour soft tissue sarcoma (STS) whose disease progresses during or after chemotherapy with doxorubicin or ifosfamide have few options and very limited life expectancy. In this setting, the DNA and transcription interacting agent trabectedin (ecteinascidin-743), isolated originally from the tunicate Ecteinascidia turbinata, has encouraging activity and is now approved in the European Union.
To review evidence for the efficacy of trabectedin in STSs.
This review includes material known to the authors through preclinical and clinical work with trabectedin, and information from relevant papers and abstracts.
Pooled analysis of Phase II studies suggests that around 50% of STS patients, failing conventional chemotherapy, experienced long lasting tumour control (either objective response or stabilization of disease) when treated with trabectedin. Twenty-nine per cent of patients were alive at 2 years, and median overall survival was 10.3 months. Leiomyosarcomas and liposarcomas appear particularly sensitive to the drug. In myxoid and round-cell liposarcomas trabectedin seems exceptionally active. A link between specific translocations underlying this disease and the drug's mechanism of action is being explored. Trabectedin is also active in synovial, ewing sarcoma and other translocation-related STSs. Trabectedin is not cardio- or neurotoxic. The neutropenia and hepatic toxicity that occur are non-cumulative, reversible, and lessened by steroid premedication. The lack of cumulative toxicities could make trabectedin appropriate for prolonged treatment.
The potential of trabectedin should be further explored in STSs in general and in specific subtypes, both in combination with other cytotoxic agents and with modulators of intracellular signalling.
Marine pharmacology, the pharmacology of marine natural products, has been for some time more associated with marine natural products chemistry rather than mainstay pharmacology. However, in recent years a renaissance has occurred in this area of research, and has seen the US Food & Drug Administration (FDA) approval in 2004 of Prialt (ziconotide, omega-conotoxin MVIIA) the synthetic equivalent of a conopeptide found in marine snails, used for the management of severe chronic pain. Furthermore Yondelis) (trabectedin, ET-743) an antitumor agent scovered in a marine colonial tunicate, and now produced synthetically, receiving Orphan Drug designation from the European Commission (EC) and FDA for soft tissue sarcomas and ovarian cancer and its registration in 2007 in the EU for the treatment of soft tissue sarcoma. The approval/marketing of so few marine natural products has come after many years of research primarily by the academic community and the sporadic involvement of major pharmaceutical companies. This commentary, through the opinions provided by several leaders in the marine natural products field, will examine the potential reasons and perceptions from both the academic and pharmaceutical communities regarding the development of marine natural products as viable therapeutic entities.
The objective of the present work was to describe an aerobic, mesophilic and heterotrophic marine bacterium, designated HYD657, able to produce an exopolysaccharide (EPS). It was isolated from a East Pacific Rise deep-sea hydrothermal vent polychaete annelid.
This micro-organism, on the basis of the phenotypical features and genotypic investigations, can be clearly assigned to the Alteromonas macleodii species and the name A. macleodii subsp. fijiensis biovar deepsane is proposed. Optimal growth occurs between 30 and 35 degrees C, at pH between 6.5 and 7.5 and at ionic strengths between 20 and 40 g x l(-1) NaCl. The G + C content of DNA was 46.5%. This bacterium excreted, under laboratory conditions, an EPS consisting of glucose, galactose, rhamnose, fucose and mannose as neutral sugars along with glucuronic and galacturonic acids and a diacidic hexose identified as a 3-0-(1 carboxyethyl)-D-glucuronic acid. Its average molecular mass was 1.6 x 10(6) Da.
The bacterium HYD657, for which the name A. macleodii subsp. fijiensis biovar deepsane is proposed, produces an unusual EPS in specific medium.
Due to its interesting biological activities, applications have been found in cosmetics. Its probable contribution to the filamentous microbial mat in the Alvinella pompejana microenvironment can be also mentioned.
Worldwide a large number of patients suffer from severe chronic pain even after treatment with opioids following the 3-step analgesic ladder developed by the WHO. Intraspinal agents, including morphine, have been tried as a fourth step. However, approximately 20% of cases remain refractory. Ziconotide, an intrathecal analgesic with orphan drug status, is a novel alternative for the management of chronic intractable pain. Ziconotide is a synthetic peptide based on the toxin of the fish-hunting marine snail, Conus magus. It is the first therapeutic agent in a new pharmacological class of "topically" active analgesics that selectively target neuron-specific (N-type), voltage-gated calcium channels. Ziconotide produces potent analgesia by interruption of Ca-dependent primary afferent transmission of pain signals in the spinal cord. Ziconotide was significantly more effective than placebo in the treatment of chronic malignant (p < 0.001) and non-malignant pain (p < 0.001). In several clinical studies morphine dosages could be substituted by ziconotide. The drug has a lag-time for the onset and offset of analgesia and adverse effects. Initial doses should therefore be low (2.4 microg/day) and titrated slowly (increasing up to a maximum of 21.6 microg/day in increases of 2.4 microg/day no more than twice weekly). The gradual increase in dose helps to reduce the incidence and severity of adverse events which affect primarily the central nervous system (e.g. dizziness, nausea, confusion). Ziconotide maintains its analgesic efficacy over months and does not cause tolerance, dependence or respiratory depression. Following intrathecal infusion ziconotide is distributed within the cerebral spinal fluid (CSF) where its clearance (0.38 ml/min) corresponds to the rate of turnover of the CSF. Negligible amounts of ziconotide are present in the systemic circulation where it is rapidly degraded by proteolysis. In conclusion, ziconotide is a new and valuable alternative analgesic for the acute and long-term treatment of severe pain, especially in patients refractory to opioids.
Linking oceans and human health: a strategic research priority for Europe
- Marine European
- Board
European Marine Board (2013) Linking oceans and human health: a strategic research priority for Europe. Ostend: Position paper 19 of the
European Marine Board.
Drug development: the journey of a medicine from lab to shelf
- I Torjesen
Torjesen I. (2015) Drug development: the journey of a medicine from lab
to shelf. Pharmaceutical Journal. http://www.pharmaceutical-journal.
com/PJ-March-2015-online/926.issue.
A historical overview of natural products in drug discovery
- D A Dias
- S Urban
- U Roessner
Dias D.A., Urban S. and Roessner U. (2012) A historical overview of
natural products in drug discovery. Metabolites 2, 303-336.