Article

Antifungal Activity of Metabolites from the Marine Sponges Amphimedon sp and Monanchora arbuscula against Aspergillus flavus Strains Isolated from Peanuts (Arachis hypogaea)

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Abstract

Contamination of preharvest and stored peanuts (Arachis hypogaea L.) by aflatoxigenic strains of Aspergillus flavus is an important economical and food safety problem in many tropical and subtropical areas of the world. The present investigation reports the antifungal activity of a halitoxins/amphitoxins enriched extract obtained from the sponge Amphimedon sp. (HAEEAsp), and of batzelladine L isolated from the sponge Monanchora arbuscula on Aspergillus flavus isolated from stored peanuts. A PCR system directed against the ITS region and aflatoxin biosynthetic pathway genes of A. flavus was applied for identification of aflatoxin producing strains. The HAEEAsp extract and batzelladine L showed minimal inhibitory concentration (MIC) in the range between 1.9 to 15.6 microg/mL and between 1.9 to 7.8 microg/mL, respectively. The minimal fungicide concentration (MFC) of HAEEAsp extract and batzelladine L was in the range between 3.9 to 31.3 microg/mL and 3.9 to 15.6 microg/mL, respectively. These results indicate that these marine alkaloids may be further explored for the development of potential lead compounds active against aflatoxigenic fungi.

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... In fact, such a tricyclic structural skeleton lacked only two spiro ether rings compared with that of pentacyclic MGAs, and thus these tricyclic MGAs were considered to be the precursor of the related pentacyclic ones (Figure 3). In 2011, by using a bioassay-guided approach, Costa-Lotufo and co-workers isolated five known tricyclic MGAs, i.e., mirabilin B (21), 8bβ-hydroxyptilocaulin (22), ptilocaulin (23), and a mixture of the 8β-and 8α-epimers of 8hydroxymirabilin B (24 and 25), from M. arbuscula colonies collected off the coast of Ceará State, Brazil, at a depth of 18 m [21]. The authors focused on the biological investigation of the isolates. ...
... In fact, such a tricyclic structural skeleton lacked only two spiro ether rings compared with that of pentacyclic MGAs, and thus these tricyclic MGAs were considered to be the precursor of the related pentacyclic ones (Figure 3). In 2011, by using a bioassay-guided approach, Costa-Lotufo and co-workers isolated five known tricyclic MGAs, i.e., mirabilin B (21), 8bβ-hydroxyptilocaulin (22), ptilocaulin (23), and a mixture of the 8β-and 8α-epimers of 8 17.69, and 7.58 µM, respectively. Neither compound 22 nor compound 23 showed cytotoxicity against PBMC, which warrants further study. ...
... Monanchora sponges are rich in batzelladines. In 2014, batzelladine L (26) was isolated from M. arbuscula and was found to have antifungal activity against Aspergillus flavus strains with minimal inhibitory concentration (MIC) values ranging from 1.9 to 7.8 µg/mL and minimal fungicide concentrations (MFCs) ranging from 3.9 to 15.6 µg/mL [23]. These results indicated that batzelladines are potential drug leads against aflatoxigenic fungi. ...
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... The structure of amphitoxin differs from that of halitoxin in that it has an additional carbon-carbon double bond in the alkyl chain that joins the pyridinium rings. Their similar structures make separation difficult and all attempts to separate this mixture were unsuccessful [46,[53][54][55]. Subfraction R4H2 displayed higher antibacterial activity than fraction R4, yielding a MIC value of 2-4 mg/L for different strains of A. baumannii, K. pneumoniae, and P. aeruginosa and a MIC value of 1 mg/L for both strains of S. aureus (Tables 2 and 3). ...
... [37] Cliona varians (EY18-3) Progreso, Yucatan No observed antibacterial activity against E. coli or C. violaceum. [37] Order [43][44][45][46] Niphates digitalis (E15) ...
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... crambescidins, batzelladines, batzellamids, hemybatzelladines, arbusculidine, monalidine; e.g. Tavares et al. 1994Tavares et al. , 1995Patil et al. 1995;van Soest et al. 1996;Braekman et al. 2000;Ferreira et al. 2011;Arevabini et al. 2014;Santos et al. 2015). Most of these compounds have potential for the treatment of severe human diseases, with many biological properties, e.g. ...
... Other secondary metabolities of the same family, i.e. batzelladines K-N, have already been isolated from M. arbuscula (e.g. Hua et al. 2007 as M. unguifera;Arevabini et al. 2014;Santos et al. 2015). Hence, the value of chemical criteria for species recognition should be revised, including other species belonging to Crambeidae and the microorganisms that they host. ...
Article
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... Guanidinederived alkaloids (Dyshlovoy et al. 2016), showing the wide scope of biological activities, e.i. anti-parasitic (Santos et al. 2015), anticancer and antibacterial (Gogineni et al. 2020), antiviral (Hua et al. 2007), antifungal (Arevabini et al. 2014), and cytotoxic (El-Demerdash et al. 2016). The potential sources of natural products in Indonesia so far have not been well explored. ...
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... Les bromotyrosines présentent une grande diversité d'activités biologiques. Elles possèdent ainsi un large éventail d'activités anti-infectieuses : antibactériennes (126), antivirales (127), antifongiques (114), antiparasitaires (128). Certaines d'entre elles possèdent également des activités anticancéreuses (104,106,128). ...
Thesis
Les biofilms microbiens peuvent avoir des conséquences néfastes dans des domaines aussi divers que les activités marines ou le domaine biomédical. Ce travail a été entrepris afin d'approfondir les résultats obtenus avec des analogues d'hémibastadines à noyau 1,2,3-triazole. Il a porté sur des composés de cette famille résultant de variations de structures approfondies. Les essais menés ont permis de confirmer que ces composés sont bien actifs comme inhibiteurs de formation de biofilms sans activité antibactérienne, même lorsqu'il s'agit de biofilms multi-souches. Cependant, les tests ont montré leur toxicité vis-à-vis du phyto et du zooplancton. Les études de relation structures­ activité ont permis de déterminer les éléments favorables l'activité anti-biofilm : nécessité de la présence d'au moins un hydroxyle phénolique sur l'un des noyaux aromatiques, intérêt des atomes de brome, perte d'activité lorsqu'il y a présence de chaînes alkylamines. En plus des bactéries marines, des essais ont également été menés sur des biofilms formés par une souche clinique de Candida albicans. Ils ont montré que ces composés sont également actifs comme inhibiteurs de formation de biofilms de cette levure, toujours sans activité antifongique.
... Further, many antifungal compounds Hippolachin A [168], (-)-agelasidine F and C [169], Puupehenone [170], Geodisterol-3-O-sulfite and 29-demethylgeodisterol-3-Osulfite [171] isolated from different sponges were also reported. Likewise, many antifungal compounds Epiplakinic acid F [172], Theonellamide TNMF [173], Batzelladine L [174] and Massadine [175], which were isolated from marine sponges, showed important properties towards many human pathogens. The crude extract of Trichoderma orientale mycelium showed a promising new and efficient antifungal drug in the treatment of candidiasis, while controlling toxicity [176]. ...
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... The alkaloid batzelladine L (91), isolated from the Brazilian sponge Monanchora arbuscular (Fig. 26), showed antifungal activity against different A. flavus strains, with MIC values ranging from 1.9 to 15.6 mg/mL and MFC values of 3.9e15.6 mg/mL [141]. (À)-Untenospongin B (92) was isolated from the antifungal extract of the marine sponge Hippospongia communis, collected from the Atlantic Coast of Morocco (Fig. 27). ...
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Grain legumes continue to occupy an important place in human nutrition as sources of protein, vitamins and minerals. From a nutritional point of view chickpea, pigeonpea, mung bean, urd bean, cowpea, lentil, soybean and peanut are the important grain legumes for the millions of people in semi-arid and tropical regions of many Asian and African countries. These legumes are used in various food forms after suitable processing depending on the regions of their production and consumption. Such aspects as production and consumption, processing and food uses, chemical composition, and effects of processing on the nutritive value of these legumes are the important topics of this paper. To enhance their utilization, new potential and diversified food uses have been highlighted. Future research needs and priority areas are listed to improve their utilization and nutritional quality.
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During the last 30 years, a number of simple 3-alkylpyridine and 3-alkylpyridinium (3-AP) compounds have been isolated from marine sponges belonging to the order Haplosclerida, suggesting these compounds as chemical markers for systematic determination of haplosclerid sponges. They were isolated from haplosclerid sponges either as (i) monomers differing in the length, saturation, branching and termination of the alkyl chains, (ii) cyclic or linear oligomers, or (iii) a mixture of high-molecular weight polymers. What the biosynthetic pathways are in marine sponges, and how these compounds can be made by organic synthesis is also an interesting question addressed in our review. In this regard we focus particularly on organic syntheses by which selective polymerization of 3-alkylpyridinium polymers may be achieved. Structural investigation of alkylpyridinium compounds and the role played by mass spectrometry has also been reviewed. In spite of their relatively simple chemical structure, all these compounds exert a broad spectrum of biological activities. More than 40 monomeric 3-AP compounds have been isolated from marine sponges and the majority bear a nitrogenous functionality at the end of the alkyl chain. Almost all reported 3-AP monomers exert moderate cytotoxicity, in the concentration range of a few micrograms per millilitre, against certain transformed cell lines. An example of 3-alkylpyridines is niphatyne A, from the marine sponge of the genus Niphates which exhibits an IC50 of 0.5 μg/mL against several transformed cell lines. The majority of 3-AP dimers and trimers were isolated from haplosclerid sponges in cyclic forms. Haliclamines are a typical representative of this group. They inhibit the division of fertilized sea urchin eggs as well as the growth of several transformed cell lines. On the other hand cyclostellettamines are typical example of cyclic alkylpyridinium dimers that modulate muscarinic receptors. Recently an increasing number of polymeric alkylpyridinium compounds have been isolated from haplosclerid sponges. Halitoxins, amphitoxins and alkylpyridinium salts from Mediterranean sponge Reniera sarai are the most studied. The latter exhibit a plethora of interesting biological activities. For instance, they are able to make pores in membranes through which DNA can be transfected into the cell, show selective cytotoxic activity against certain human cancer cells and possess non-toxic inhibitory antifouling properties against larvae of several important fouling organisms. The biological activities and potential use of alkylpyridinium polymers are discussed.
Article
L’extrait méthanolique de l’éponge marine Haliclona exigua montre une activité antifongique prometteuse in vitro contre Candida albicans (CMI = 7,8 μg/ml), Cryptococcus neoformans (CMI = 31,2 μg/ml), Sporothrix schenckii (CMI = 31,2 μg/ml), Trichophyton mentagrophytes (CMI = 31,2 μg/ml), Aspergillus fumigatus (31,2 μg/ml) and Candida parapsilosis (CMI = 7,8 μg/ml). Après fractionnement de l’extrait méthanolique en quatre fractions, l’activité antifongique a été détectée exclusivement dans les fractions hexane-soluble et chloroforme-soluble. Ces deux fractions ont été réunies et leur composant le plus actif a été purifié. Il a été identifié à l’araguspongine C qui a montré une activité antifongique intéressante contre Cryptococcus neoformans, Sporothrix schenckii, Aspergillus fumigatus et Trichophyton mentagrophytes avec des CMI identiques (50 μg/ml).
Article
A complex mixture of high molecular weight toxic pyridinium salts designated halitoxin has been isolated from the sponges Haliclona rubens, H. viridis, and H. erina. The toxin has been separated into molecular weight range fractions of 500-1000, 1000-25 000, and > 25 000, each of which shows the same spectral and biological properties. A general structure for halitoxin has been proposed based on 1H and 13C NMR analyses and identification of a group of 3-alkenylpyridines obtained in good yield upon pyrolysis of the toxin. The oligomeric/polymeric toxin consists of 3-alkylpyridine units connected by the nitrogen of one ring and the terminus of the 3-alkyl chain of the next. No functionality other than the pyridinium ring has been detected. Halitoxin is cytotoxic, haemolytic, and toxic to fish and mice.
Article
An inhibitor of the epidermal growth factor (EGF) receptor was isolated from an extract of the Micronesian sponge Callyspongia fibrosa. The structure of the EGF-active compound was first proposed, on the basis of ion-spray mass spectrometry, to be the cyclic dimer 1 (n = 2) but comparison of a sample produced by an efficient synthetic route revealed that hypothesis to be incorrect. The EGF-active constituent must therefore be a large oligomer or a polymer of the same repeating subunit 1.
Chapter
Marine sponges have been asource of avariety of polycyclic diamine alkaloids presenting different skeletal types, such as the halicyclamines, `upenamide, xestospongins, araguspongines, halicyclamines, haliclonacyclamines, arenosclerins, ingenamines, and madangamines. The occurrence of these alkaloids in sponges is quite possibly due to their biogenetic relatedness. Since these alkaloids also display different biological activities, they have been an interesting target in organic synthesis. The review includes the occurrence, isolation and structure determination, biological activities, and biogenetic relationships as well as the total synthesis of polycyclic diamine alkaloids isolated from marine sponges.
Article
The peer-reviewed marine pharmacology literature in 2007-8 is covered in this review, which follows a similar format to the previous 1998-2006 reviews of this series. The preclinical pharmacology of structurally characterized marine compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 74 marine natural products. Additionally, 59 marine compounds were reported to affect the cardiovascular, immune and nervous systems as well as to possess anti-inflammatory effects. Finally, 65 marine metabolites were shown to bind to a variety of receptors and miscellaneous molecular targets, and thus upon further completion of mechanism of action studies, will contribute to several pharmacological classes. Marine pharmacology research during 2007-8 remained a global enterprise, with researchers from 26 countries, and the United States, contributing to the preclinical pharmacology of 197 marine compounds which are part of the preclinical marine pharmaceuticals pipeline. Sustained preclinical research with marine natural products demonstrating novel pharmacological activities, will probably result in the expansion of the current marine pharmaceutical clinical pipeline, which currently consists of 13 marine natural products, analogs or derivatives targeting a limited number of disease categories.
Article
A new polymeric pyridinium alkaloid named amphitoxin [2] has been isolated from Amphimedon compressa, and its structure determined by spectroscopic analysis. In laboratory feeding experiments, crude extracts and purified amphitoxin [2] from A. compressa at lower than natural concentration levels effectively deterred feeding of a generalist predatory Caribbean reef fish, Thalassoma bifasciatum.
Article
From the marine sponge Reniera sarai 3-alkylpyridinium oligomers and polymers have been isolated. 3-Alkylpyridinium polymers are potent anticholinesterase agents; in addition, they show hemolytic and cytotoxic activities. Oligomers with a molecular weight lower than 3000 Da do not possess any significant activity. We report structural characterization of 3-alkylpyridinium polymers and their behavior in aqueous solutions. We found that biologically active polymers are composed of head-to-tail 3-alkylpyridinium units. According to MALDI-TOF spectrometry two species of polymers exist, the smaller with a molecular weight of 5520 Da and the larger with a molecular weight of 18,900 Da. Both polymers are soluble only in water, while low molecular oligomers are readily soluble in organic solvents. Polymers form large water-dissolved supramolecular structures with an average hydrodynamic radius of 23 +/- 2 nm and, therefore, cannot be separated with size-exclusion chromatography.
Article
In the past decade, the frequency of diagnosed fungal infections has risen sharply due to several factors, including the increase in the number of immunosuppressed patients resulting from the AIDS epidemic and treatments during and after organ and bone marrow transplants. Linked with the increase in fungal infections is a recent increase in the frequency with which these infections are recalcitrant to standard antifungal therapy. This review summarizes the factors that contribute to antifungal drug resistance on three levels: (i) clinical factors that result in the inability to successfully treat refractory disease; (ii) cellular factors associated with a resistant fungal strain; and (iii) molecular factors that are ultimately responsible for the resistance phenotype in the cell. Many of the clinical factors that contribute to resistance are associated with the immune status of the patient, with the pharmacology of the drugs, or with the degree or type of fungal infection present. At a cellular level, antifungal drug resistance can be the result of replacement of a susceptible strain with a more resistant strain or species or the alteration of an endogenous strain (by mutation or gene expression) to a resistant phenotype. The molecular mechanisms of resistance that have been identified to date in Candida albicans include overexpression of two types of efflux pumps, overexpression or mutation of the target enzyme, and alteration of other enzymes in the same biosynthetic pathway as the target enzyme. Since the study of antifungal drug resistance is relatively new, other factors that may also contribute to resistance are discussed.
The halitoxin complex from the marine sponge Amphimedon viridis, collected in the São Sebastião channel (southeastern Brazilian coast), was isolated by gel-filtration chromatography on Sephadex LH-20. Spectroscopic data (1H, 13C and 2D-NMR) of halitoxin from A. viridis indicated that it has the same two alkylpyridine monomers composition of the previously isolated halitoxin from Amphimedon compressa (as Haliclona rubens). Nevertheless, analysis by High Performance Gel Permeation Chromatography indicated that the halitoxin complex of A. viridis has a lower molecular weight (500, 2000 and 5000 Da; the major component corresponding to the fraction of 2000 Da MW) when compared to the previously isolated halitoxin complex from A. compressa. Some pharmacological properties of the halitoxin complex from A. viridis were evaluated in terms of lethality, antimitosis, hemolysis and neurotoxicity. The possible chemotaxonomic value of alkyl pyridine alkaloids is discussed.
Article
Aflatoxins are toxic and extremely carcinogenic natural secondary metabolites produced primarily by the fungi Aspergillus flavus and Aspergillus parasiticus. The biosynthesis of aflatoxins is a complex process involving multi-enzymatic reactions. Genetic studies of the molecular mechanism of aflatoxin B1 biosynthesis have identified an aflatoxin pathway gene cluster of 70 kilobase pairs in length consisting of at least 24 identified structural genes including a positive regulatory gene as transcription activator. The structural genes encode cytochrome P450 monooxygenases, dehydrogenases, oxidases, methyltransferases, a polyketide synthase and two unique fatty acid synthases. The aflatoxin biosynthesis and its genetic regulation are discussed in this review. The current knowledge of the relationship between fungal development and secondary metabolism is also summarized.
Article
Aspergillus flavus is an imperfect filamentous fungus that is an opportunistic pathogen causing invasive and non-invasive aspergillosis in humans, animals, and insects. It also causes allergic reactions in humans. A. flavus infects agricultural crops and stored grains and produces the most toxic and potent carcinogic metabolites such as aflatoxins and other mycotoxins. Breakthroughs in A. flavus genomics may lead to improvement in human health, food safety, and agricultural economy. The availability of A. flavus genomic data marks a new era in research for fungal biology, medical mycology, agricultural ecology, pathogenicity, mycotoxin biosynthesis, and evolution. The availability of whole genome microarrays has equipped scientists with a new powerful tool for studying gene expression under specific conditions. They can be used to identify genes responsible for mycotoxin biosynthesis and for fungal infection in humans, animals and plants. A. flavus genomics is expected to advance the development of therapeutic drugs and to provide information for devising strategies in controlling diseases of humans and other animals. Further, it will provide vital clues for engineering commercial crops resistant to fungal infection by incorporating antifungal genes that may prevent aflatoxin contamination of agricultural harvest.
Article
Contamination of peanuts with mycotoxins, particularly aflatoxins, is a worldwide problem that affects both food safety and agricultural economies. Most countries have adopted regulations that limit the quantity of aflatoxins in food and feed to 20 microg kg(-1) or less; however, environmental conditions in most of the world where peanuts are produced and stored often make it difficult or impossible to attain such low concentrations. In addition to aflatoxins, peanuts are often contaminated with cyclopiazonic acid (CPA). Both mycotoxins are produced by Aspergillus flavus, a ubiquitous fungus that can infect and grow in peanuts under both pre- and post-harvest conditions. Management of mycotoxin contamination in peanuts generally involves removal of high-risk components from shelled lots or the removal of individual, highly contaminated nuts. This is accomplished by various processes such as screening, kernel sizing, electronic colour sorting, hand sorting, and blanching followed by electronic colour sorting. Recently, biological control technology has been developed that prevents much of the contamination that might otherwise occur. Biocontrol is based on competitive exclusion whereby a dominant population of a non-toxigenic strain of A. flavus is established in the soil before peanuts are subjected to conditions favouring contamination. The applied strain competes with toxigenic strains for infection sites, resulting in significantly reduced concentrations of aflatoxins in peanuts. Monitoring of the first commercial use of the technology showed that aflatoxins were reduced by an average of 85% in farmers' stock peanuts and by as much as 98% in shelled, edible grade peanuts.
Agricultural crop production statistics
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FAO. (2011) Agricultural crop production statistics, 2011.
Reference method for broth dilution antifungal susceptibility testing of filamentous fungi: approved standard
Clinical and Laboratory Standards Institute. (2008) Reference method for broth dilution antifungal susceptibility testing of filamentous fungi: approved standard,, Clinical and Laboratory Standards Institute, Wayne, PA. Natural Product Communications 2014