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Isorawsonol and Related IMP Dehydrogenase Inhibitors from the Tropical Green Alga Avrainvillea rawsonii
Abstract
Guided by inhibitory activity against IMP dehydrogenase (IMPDH), a new brominated diphenylmethane derivative, isorawsonol, has been isolated from the tropical green alga Avrainvillea rawsonii. Its structure was determined by detailed spectroscopic analysis including HMQC and HMBC. The known metabolites, avrainvilleol, avrainvilleol methyl ether, 3-bromo-4,5-dihydroxylbenzyl alcohol, and rawsonol, were also isolated from this alga and two of these showed a modest ability to inhibit IMPDH. The formation of isorawsonol is envisioned as being similar to that of rawsonol involving condensation of two molecules of avrainvilleol.
... One can imagine that 1 might form a highly reactive para-quinone methide under acidic conditions leading to decomposition. Luckily, spectroscopic data of naturally occurring 1 in d 6 -acetone have also been reported, 19 and the spectral data for synthetic 1 ( 1 H and 13 C NMR) were identical with those previously reported. 10,19 This work shows the promise of the transition-metal-free coupling of readily available boronic acids and tosylhydrazones to prepare complex, biologically active diarylmethanes. ...
... Luckily, spectroscopic data of naturally occurring 1 in d 6 -acetone have also been reported, 19 and the spectral data for synthetic 1 ( 1 H and 13 C NMR) were identical with those previously reported. 10,19 This work shows the promise of the transition-metal-free coupling of readily available boronic acids and tosylhydrazones to prepare complex, biologically active diarylmethanes. Specifically, the synthesis of avrainvilleol was completed in six steps (longest linear sequence) starting with commercially available vanillyl alcohol. ...
... NaHCO 3 (10 mL) and brine (10 mL), dried (Na 2 SO 4 ), and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with EtOAc/ hexane (1:19) to give 66 mg (58%) of 8 as a colorless oil that solidified upon standing; 1 4-Bromo-3-hydroxy-2-methoxy-6-(methoxymethyl)benzaldehyde (19). A solution of bromine in AcOH (5.1 mL, 1 M, 5.1 mmol) was added dropwise to a solution of 3-hydroxy-2-methoxy-6-(methoxymethyl)benzaldehyde (18) 17 (1.00 ...
The first total synthesis of the marine natural product avrainvilleol is reported. The total synthesis features the first application of the transition metal-free coupling of a tosyl hydrazone and a boronic acid to the preparation of a complex natural product, and the first example of this coupling with a hindered di-ortho substituted hydrazone substrate.
... Avrainvillea cf digitata also showed high cytotoxic and antiproliferative activity against KB cells. This result concurs with previous studies in which Avrainvillea species have been shown to produce isorawsonol, a brominated diphenylmethane derivative, related to the inhibition of cell proliferation (Chen et al. 1994). Additionally, antimitotic glycoglycerolipids play an important role in cell cycle arrest in human cancer cells and have been isolated from this genus (Williams et al. 2007), suggesting that Avrainvillea could be used for the isolation of antiproliferatve compounds. ...
... Por otro lado, A. cf digitata mostró también una alta actividad citotóxica y antiproliferativa sobre células KB. Este resultado es similar al obtenido en estudios previos donde diferentes especies de Avrainvillea han mostrado que producen isorawsonol, un derivado brominado del difenilmetano que se relaciona con la inhibición de la proliferación celular(Chen et al. 1994). Adicionalmente, los antimitóticos glicoglicerolípidos, que juegan un papel importante en el retraso del ciclo celular en células de cáncer humano, han sido aislados de especies de este genero(Williams et al. 2007), lo que suigiere que Avrainvillea podría ser usada para el aislamiento de compuestos antiproliferativos.En cuanto a la alta citotoxicidad mostrada por las dos especies de Penicillus de Yucatán, no existe a la fecha ningún otro estudio donde se reporten actividades similares a las encontradas en el presente estudio. ...
Extracts from 27 marine algal species (14 Rhodophyta, 5 Phaeophyta, and 8 Chlorophyta) from the Yucatán Peninsula (Mexico) were evaluated for cytotoxic and antiproliferative activity by 3(4,5-dimethylthiazole-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays, respectively. To determine the specificity of cytotoxic activity against tumor cells, the selective index (SI) was also calculated. The following cancer cell lines were employed: normal canine kidney (MDCK) cells, human laryngeal carcinoma (Hep-2) cells, human cervical adenocarcinoma (HeLa) cells, and human nasopharyngeal carcinoma (KB) cells. The results indicated that 44% and 51% of the algal species tested showed cytotoxic and antiproliferative activity, respectively. Most of the cytotoxic extracts were from species of Chlorophyta, with Udotea flabellum and U. conglutinate showing the highest cytotoxic activity against all the cancer cell lines. For Rhodophyta, the Bryothamnion triquetrum extract showed outstanding selective cytotoxicity against Hep-2 cells (CC50 8.29 µg mL–1, SI = 12.04). Two of the five species of Phaeophyta tested (Lobophora variegata and Dictyota caribaea) showed high cytotoxicity activity against the KB cell line. The data show that these species are a potential source of compounds for the treatment of certain cancer diseases.
... Bioassay-guided fractionation utilizing inhibitory activity against inosine -5 -monophosphate dehydrogenase inhibitor (IMPDH) leads to the isolation of a new brominated diphenylmethane derivative. Isorawsonol 10 was isolated from the tropical green alga Arrainvilla rawsonii by Chen and colleagues in 1994 (Chen et al., 1994). The activity of IMPDH has been linked with cellular proliferation and inhibition of that enzyme has been demonstrated to have anticancer and immunosuppressive effects (Chen et al., 1994). ...
... Isorawsonol 10 was isolated from the tropical green alga Arrainvilla rawsonii by Chen and colleagues in 1994 (Chen et al., 1994). The activity of IMPDH has been linked with cellular proliferation and inhibition of that enzyme has been demonstrated to have anticancer and immunosuppressive effects (Chen et al., 1994). ...
... Bioassay-guided fractionation utilizing inhibitory activity against inosine -5 -monophosphate dehydrogenase inhibitor (IMPDH) leads to the isolation of a new brominated diphenylmethane derivative. Isorawsonol 10 was isolated from the tropical green alga Arrainvilla rawsonii by Chen and colleagues in 1994 (Chen et al., 1994). The activity of IMPDH has been linked with cellular proliferation and inhibition of that enzyme has been demonstrated to have anticancer and immunosuppressive effects (Chen et al., 1994). ...
... Isorawsonol 10 was isolated from the tropical green alga Arrainvilla rawsonii by Chen and colleagues in 1994 (Chen et al., 1994). The activity of IMPDH has been linked with cellular proliferation and inhibition of that enzyme has been demonstrated to have anticancer and immunosuppressive effects (Chen et al., 1994). ...
... Avrainvillea cf digitata also showed high cytotoxic and antiproliferative activity against KB cells. This result concurs with previous studies in which Avrainvillea species have been shown to produce isorawsonol, a brominated diphenylmethane derivative, related to the inhibition of cell proliferation (Chen et al. 1994). Additionally, antimitotic glycoglycerolipids play an important role in cell cycle arrest in human cancer cells and have been isolated from this genus (Williams et al. 2007), suggesting that Avrainvillea could be used for the isolation of antiproliferatve compounds. ...
... Por otro lado, A. cf digitata mostró también una alta actividad citotóxica y antiproliferativa sobre células KB. Este resultado es similar al obtenido en estudios previos donde diferentes especies de Avrainvillea han mostrado que producen isorawsonol, un derivado brominado del difenilmetano que se relaciona con la inhibición de la proliferación celular(Chen et al. 1994). Adicionalmente, los antimitóticos glicoglicerolípidos, que juegan un papel importante en el retraso del ciclo celular en células de cáncer humano, han sido aislados de especies de este genero(Williams et al. 2007), lo que suigiere que Avrainvillea podría ser usada para el aislamiento de compuestos antiproliferativos.En cuanto a la alta citotoxicidad mostrada por las dos especies de Penicillus de Yucatán, no existe a la fecha ningún otro estudio donde se reporten actividades similares a las encontradas en el presente estudio. ...
Extracts from 27 marine algal species (14 Rhodophyta, 5 Phaeophyta, and 8 Chlorophyta) from the Yucatán Peninsula (Mexico) were evaluated for cytotoxic and antiproliferative activity by 3(4,5dimethylthiazole2yl)2,5diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays, respectively. To determine the specificity of cytotoxic activity against tumor cells, the selective index (SI) was also calculated. The following cancer cell lines were employed: normal canine kidney (MDCK) cells, human laryngeal carcinoma (Hep2) cells, human cervical adenocarcinoma (HeLa) cells, and human nasopharyngeal carcinoma (KB) cells. The results indicated that 44% and 51% of the algal species tested showed cytotoxic and antiproliferative activity, respectively. Most of the cytotoxic extracts were from species of Chlorophyta, with Udotea flabellum and U. conglutinate showing the highest cytotoxic activity against all the cancer cell lines. For Rhodophyta, the Bryothamnion triquetrum extract showed outstanding selective cytotoxicity against Hep2 cells (CC50 8.29 µg mL1, SI = 12.04). Two of the five species of Phaeophyta tested (Lobophora variegata and Dictyota caribaea) showed high cytotoxicity activity against the KB cell line. The data show that these species are a potential source of compounds for the treatment of certain cancer diseases.
... Another metabolic compound, 6-deoxy-6-aminoglucoglycerolipid, has been isolated from the organic extract of A. nigricans from the Dominican Republic (Andersen and Taglialatela-Scafati 2005) and two molecules (rawsonal and isorawsonol) were isolated from A. rawsonii (Dickie) Howe. The molecules found in A. rawsonii are probably formed by the condensation of two molecules of avrainvilleol (Chen et al. 1994), a compound that is toxic to fishes and exhibits antibacterial and anti-herbivore activities (Sun et al. 1983). Besides inhibiting consumption by reef fishes, avrainvilleol also protects the associated crab Thersandrus compressus Desbonne and the gastropod Costasiella ocellifera Simroth from predatory fish (Hay et al. 1990). ...
... Defensive chemicals produced by Avrainvillea elliottii had not been isolated and identified prior to our study, but it is likely that avrainvilleol or a similar compound was responsible for deterring Lytechinus variegatus consumption. Secondary metabolites similar to avrainvilleol have previously been isolated from Avrainvillea species, including A. longicaulis (Kü tzing) G. Murray et Boodle (Hay et al. 1990), A. nigricans (Colon et al. 1987, Andersen andTaglialatela-Scafati 2005), and A. rawsonii (Chen et al. 1994). ...
This study tested potential chemical defense of the green seaweed Avrainvillea elliottii against grazing by the sea urchin Lytechinus variegatus. We examined intraspecific variation of defensive chemicals in different parts of the thallus (margin, blade and stipe). We predicted that thal- lus parts making the greatest contributions to thallus fit- ness would show the greatest chemical deterrence to herbivory. The susceptibility of the whole alga and its dif- ferent parts to consumption by L. variegatus was evalu- ated using assays consisting of powdered algae treated with natural concentrations of crude A. elliottii extract. Results from feeding evaluations showed that the crude extracts of whole plants and different thallus parts deterred consumption by this sea urchin. The results also supported our prediction that stronger chemical defens- es occur in the more apical and younger areas of the thallus (margins), parts whose loss would result in the greatest reduction of fitness. These results provide add- ed evidence supporting the ability of siphonaceous or coenocytic green macroalgae to concentrate defensive chemicals in growing parts.
... Wall et al., 1989;Wiemer et al., 1991;Kurata et al., 1997;Xu et al., 2003;Li et al., 2008). They are also known to inhibit a variety of enzymes including phospholipase A2, 15-lipoxygenase, inosine monophosphate dehydrogenase, guanosine monophosphate and Į-glucosidase (Wiemer et al., 1991;Chen et al., 1994;Fu et al., 1995;Kurihara et al., 1999). As for antiviral activity, the literature appears to be scarce. ...
... These results agree with previous data obtained in IPNV-infected RTG-2 cells and in IPNV-infected CHSE-214 cells (Hudson et al., 1988;Jashes et al., 1996). Among literature cited above, Chen et al. (1994) and Fu et al. (1995) reported that some polybrominated bromophels significantly inhibited IMP dehydrogenase. Considering the broad antiviral activities in vitro of ribavirin as an inhibitor of IMP dehydrogenase, it is suggested that this activity could be an antiviral action-mechanisms of the two isolated bromophenols against IHNV and IPNV, although further studies on mechanismm of action of isolated two bromophenols are needed. ...
Our previous investigation revealed that 80% methanolic extract of the red alga Polysiphonia morrowii has significant antiviral activities against fish pathogenic viruses, infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV). The present study was conducted to identify compounds attributed for its antiviral activities and investigate their antiviral activities against IHNV and IPNV. Activity-guided fractionation for 80% methanolic extract of Polysiphonia morrowii using a cell-based assay measuring virus-induced cytopathic effect (CPE) on cells yielded a 90% methanolic fraction, which showed the highest antiviral activity against both viruses among fractions yielded from the extract. From the fraction, two bromophenols were isolated and identified as 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihydroxybenzaldehyde (2) based on spectroscopic analyses. For both compounds, the concentrations to inhibit 50% of flounder spleen cell (FSP cell) proliferation (CC(50)) and each viral replication (EC(50)) were measured. In the pretreatment test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihy-droxybenzaldehyde (2) exhibited significant antiviral activities showing selective index values (SI = CC(50)/EC(50)) of 20 to 42 against both IHNV and IPNV. In direct virucidal test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) showed significant antiviral activités against both viruses while 3-bromo-4,5-dihydroxybenzaldehyde (2) was significantly effective against only IHNV. Although antiviral efficacies of both compounds against IHNV and IPNV were lower than those of ribavirin used as a positive control, our findings suggested that the red alga Polysiphonia morrowii and isolated two bromophenols may have potential as a therapeutic agent against fish viral diseases.
... Gerwick and coworkers at Oregon State University evaluated over 500 extracts of marine microalgae (primarily cyanobacteria) and macroalgae for their ability to inhibit IMPDH [162]. This assay yielded twenty-four active extracts and resulted in the isolation of the bromophenolic compound isorawsonol (IC 50 = 18 μM) from the tropical marine green algae Avrainvillea rawsonii [163]. Other marine natural products isolated using this same assay system include pellynic acid (EC 50 = 1.03 μM) from the sponge Pellina triangulata [164] and bastadin alkaloids (EC 50 s from 3 to 11 μM) from the Verongid sponges Ianthella basta and I. flabelliformis [165]. ...
... In collaboration with Syntex Research, researchers at Oregon State University examined extracts and purified compounds from marine cyanobacteria and algae for inhibitors of pp60 v-src TK [reviewed in 162]. Extracts from laboratory cultures of the chrysophyte, Poterioochromonas malhamensis, inhibited pp60 v-src TK [163]. Malhamensilipin A, Fig. (14), a new C 24 hexachlorosulfolipid, was subsequently isolated and found to be a moderately weak TK inhibitor (IC 50 = 35 μM). ...
Antitumor drug discovery programs aim to identify chemical entities for use in the treatment of cancer. Many strategies have been used to achieve this objective. Natural products have always played a major role in anticancer medicine and the unique metabolites produced by marine organisms have increasingly become major players in antitumor drug discovery. Rapid advances have occurred in the understanding of tumor biology and molecular medicine. New insights into mechanisms responsible for neoplastic disease are significantly changing the general philosophical approach towards cancer treatment. Recently identified molecular targets have created exciting new means for disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance and blood supply. Such tumor-specific treatments could someday decrease our reliance on traditional cytotoxicity-based chemotherapy and provide new less toxic treatment options with significantly fewer side effects. Novel molecular targets and state-of-the-art, molecular mechanism-based screening methods have revitalized antitumor research and these changes are becoming an ever-increasing component of modern antitumor marine natural products research. This review describes marine natural products identified using tumor-specific mechanism-based assays for regulators of angiogenesis, apoptosis, cell cycle, macromolecule synthesis, mitochondrial respiration, mitosis, multidrug efflux and signal transduction. Special emphasis is placed on natural products directly discovered using molecular mechanism-based screening.
... Moreover, five new bioactive meroditerpenoids, of which three exhibited moderate cytotoxicity to NCI-H460 human lung cancer cell line (LC50 ranges from 2 to 11 µM), were isolated from Stypopodium flabelliforme in Papua New Guinea [84] . On the other hand, three new terpenoids were isolated from S. zonale, and one methyl ester presents in vitro cytotoxic activity on human lung and colon carcinoma [85] . ...
Marine plants contribute half of the global organic carbon fixation, thus play a key role in global carbon cycles. Tropical biomes are the most diverse communities, which produce numerous value-added compounds. The metabolites from tropical marine algae and plants have been utilized for the therapy of the globally threatening diseases, such as acquired immune deficiency syndrome, Dengue fever, and cancer. However, metabolite treasure underpinned by tropical marine plants is largely untapped. The bioactive nature of more compounds remain to be discovered. This mini-review examines several aspects of value-added compounds from tropical marine plants, such as microalgae, macroalgae, seagrasses, and mangroves. Biotechnological and pharmaceutical applications involving these compounds are also discussed.
... Moreover, five new bioactive meroditerpenoids, of which three exhibited moderate cytotoxicity to NCI-H460 human lung cancer cell line, were isolated from Stypopodium flabelliforme in Papua New Guinea [84] . On the other hand, three new terpenoids were isolated from S. zonale, and one methyl ester presents in vitro cytotoxic activity on human lung and colon carcinoma [85] . ...
... The resulting extracts were subjected to multiple chromatographic techniques to yield pure compounds. The identification and structural elucidation were performed using several spectrometric and spectroscopic methods, including 1D NMR ( 1 H, 13 C, and DEPT), 2D NMR (HMBC, COSY, NOESY, and HMQC), mass spectrometry and X-ray crystallography [13e16]. ...
Seaweeds have attracted attention in the past decade as a biological source of highly diverse secondary metabolites with great potential in the industrial and pharmaceutical sciences. Herein, we represent a comprehensive cheminformatics study to compare the chemical diversity of seaweed metabolites based on their taxonomic source. Seaweed Metabolite Database (SWMD) was utilized in this study. The compounds were manually categorized into three datasets, namely red algae (Rhodophyta, n=645), brown algae (Phaeophyta, n=220), and green algae (Chlorophyta, n=32). The compounds in each dataset were curated to generate six chemical descriptors of pharmaceutical interest for each molecule, which were later used to visualize the chemical space of these metabolites by principal component analysis. Scaffolds were generated by removing side chains and keeping the core part of each molecule. Scaffold diversity among the tested datasets was quantified using Cyclic System Retrieval Curves. Green algae metabolites in SWMD possessed the highest scaffold diversity followed by brown and red algae metabolites, respectively. Three structural binary fingerprints, including ECFP_4, MACCS keys, and PubChem were computed indicating that the red algae metabolites had the highest fingerprint diversity followed by the green and brown algae metabolites respectively. Finally, Consensus Diversity Plots were generated to assess the global diversity considering both scaffold and fingerprint diversity. It was concluded that green algae metabolites in the SWMD are the most diverse regarding chemical descriptors of pharmaceutical relevance and scaffolds. While red algae possess the highest fingerprint diversity.
... In 1967, the first two BPs were isolated from the red algae Rhodomela larix [3]. Over the past few decades, a great number of BPs were isolated from various marine algae species including red algae [4][5][6][7][8][9], green algae [10][11][12][13][14], and brown algae [15][16][17][18][19]. Some BPs are also found in other marine organisms such as sponges [18,[20][21][22][23][24], ascidians [25][26][27], mussels [28], polychaetes [29], and marine proteobacteria [30]. ...
Marine algae contain various bromophenols that have been shown to possess a variety of biological activities, including antiradical, antimicrobial, anticancer, antidiabetic, anti-inflammatory effects, and so on. Here, we briefly review the recent progress of these marine algae biomaterials and their derivatives from 2011 to 2020, with respect to structure, bioactivities, and their potential application as pharmaceuticals.
... HO Chlorinated and brominated derivatives are much more diversified. Many simple Cl and Br aromatics are known to be biogenic, this is the case for instance for 1,2,3,4-tetrachlorobenzene [49], 2,6dibromophenol [50], and some chlorinated phenols [51], as well as a chloro-bromo-tyrosine [52], and many polyaromatics, for instance, the tetrabromo-compound rawsonol (Scheme 5) [53,54]. ...
In this review, we examine the possibility that some halogenated organic derivatives were used in the primitive ocean at the beginning of life on Earth. First we describe the existence of extraterrestrial halogenated molecules, then we study their non-biological syntheses on the present Earth, especially in volcanic environments. In order to demonstrate the diversity of today’s halogenated biomolecules representative examples are given and the biosynthesis of some of them is summarized. Finally, we propose two aspects of the chemistry of halogenated compounds that may have been useful en route to biomolecules, firstly the use of methyl chloride as the first methylation reagent, secondly the synthesis and use of α-chlorocarbonyl derivatives.
... For instance, the crude extracts of red alga Gracilaria tenuistipitata show anti-proliferative effects on Ca9-22 oral cancer cells by inducing cellular apoptosis, DNA damage, and oxidative stress (Yeh et al. 2012), whereas crude extracts of red algae Plocamium telfairiae inhibit growth of HT-29 colon cancer cells by causing caspase-dependent apoptosis (Kim et al. 2007). Green algae: The bromophenolic compound isorawsonol, isolated from green alga Avrainvillea rawsonii and the glycolipids nigricanosides A and B, isolated from A. nigricans, induce mitotic arrest in several cancer cell lines (Chen et al. 1994;Williams et al. 2007). Caulerpenyne, a sesquiterpene isolated from the green algae Caulerpa sp., shows anti-proliferative activity against tumour cell lines SK-N-SH by modifying the microtubular network during cell division and migration (Barbier et al. 2001). ...
The sudden and uncontrolled proliferation of cells is a common cause of mortality. Cancer is a multifactorial disorder which involves both exogenous and endogenous factors for initiation, promotion and progression. The interplay between genes and environment induces genetic and epigenetic alterations to cause chronic diseases including cancers. The management of cancer is far from addressing genetic and epigenetic alterations. The major limitation of current therapy is that it affects the non-targeted tissues also. In this respect, anticancer drugs which are derived from natural resources are considered as good leads for drug development. The natural products have shown anticancer activity in various types of cancer. Thus, the use of the natural product in cancer chemotherapy is gaining attention. In this chapter, the recent plant-derived secondary metabolites with potential for therapeutic management of cancer are discussed.
... For instance, the crude extracts of red alga Gracilaria tenuistipitata show anti-proliferative effects on Ca9-22 oral cancer cells by inducing cellular apoptosis, DNA damage, and oxidative stress (Yeh et al. 2012), whereas crude extracts of red algae Plocamium telfairiae inhibit growth of HT-29 colon cancer cells by causing caspase-dependent apoptosis (Kim et al. 2007). Green algae: The bromophenolic compound isorawsonol, isolated from green alga Avrainvillea rawsonii and the glycolipids nigricanosides A and B, isolated from A. nigricans, induce mitotic arrest in several cancer cell lines (Chen et al. 1994;Williams et al. 2007). Caulerpenyne, a sesquiterpene isolated from the green algae Caulerpa sp., shows anti-proliferative activity against tumour cell lines SK-N-SH by modifying the microtubular network during cell division and migration (Barbier et al. 2001). ...
Throughout history, naturally derived molecules have had countless applications in medicine, pharmacy, and biology. This rich reservoir of natural compounds demonstrated great potential in treating various diseases, mainly cancer. Alkaloids, a subfamily of secondary metabolites, are derived from a large variety of organisms including plants, animals, and marine organisms. This group of compounds has exhibited promising anticancer and chemopreventive effects and has been found to chemo-sensitize tumor cells that are resistant to conventional chemotherapy. The remarkable structural diversity of anticancer alkaloids has allowed their use as lead compounds in the treatment of cancer. Chemical derivatization and modifications of alkaloid structures led to the improvement of their therapeutic potential. Many of these second-generation alkaloids are currently commercially available or are in advanced clinical trials, and a major group is still being tested preclinically. Here we provide an overview of alkaloids that are in clinical trials and which are FDA approved. We have classified anticancer alkaloids according to their biological origin and presented an extensive discussion of their mechanism of action and clinical toxicity. The understanding of the mechanism of action and clinical manifestations of anticancer alkaloids is essential for advancing their use and enhancing their efficacy in the clinic.
... For instance, the crude extracts of red alga Gracilaria tenuistipitata show anti-proliferative effects on Ca9-22 oral cancer cells by inducing cellular apoptosis, DNA damage, and oxidative stress (Yeh et al. 2012), whereas crude extracts of red algae Plocamium telfairiae inhibit growth of HT-29 colon cancer cells by causing caspase-dependent apoptosis (Kim et al. 2007). Green algae: The bromophenolic compound isorawsonol, isolated from green alga Avrainvillea rawsonii and the glycolipids nigricanosides A and B, isolated from A. nigricans, induce mitotic arrest in several cancer cell lines (Chen et al. 1994;Williams et al. 2007). Caulerpenyne, a sesquiterpene isolated from the green algae Caulerpa sp., shows anti-proliferative activity against tumour cell lines SK-N-SH by modifying the microtubular network during cell division and migration (Barbier et al. 2001). ...
Marine floras, constituting over 90% of the oceanic biomass, are rich sources of potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. They act as potential sources of drugs with various pharmacological properties (such as antioxidant, anti-inflammatory, antibiotic, immunostimulatory, and anticancer). Although human history depicts the use of marine floras as medicine and nutrient supplement, the search for novel pharmaceutical compounds has mostly been limited to terrestrial floras. Marine floras are taxonomically diverse, largely productive, biologically active, and chemically unique, thereby offering great scope for discovery of new anticancer drugs. The mode of action of marine flora products is through activation of macrophages, induction of apoptosis, and prevention of oxidative damage of DNA, thereby controlling carcinogenesis. This chapter focuses on the immunomodulatory and therapeutic properties of marine flora-derived products in the context of increasing cancer incidences and demand for cheaper, safer, and potent anticancer drugs. It highlights the excellent therapeutic potential of the known marine flora-derived anticancer compounds, thereby encouraging researchers to actively participate in the marine natural product drug discovery for treatment and prevention of cancer.
... 30 The geometry of all conformers within 21 kJ/mol were optimized using density functional theory (DFT) in the Gaussian D09 package, 31 using the B3LYP/6-31G(d) level of theory. Solvent interactions, either DMSO (1,13,14) or MeOH (15a, 15b), were considered with PCM. Frequencies computation was performed to ascertain true minima were obtained (zero imaginary frequency), and the resulting free energies were extracted to calculate the Boltzmann distribution. ...
A series of oligomeric phenols including the known natural product 3,4,3',4'-tetrahydroxy-1,1'-biphenyl (3), the previously synthesized 2,3,8,9-tetrahydroxybenzo[ c]chromen-6-one (4), and eight new related natural products, cladophorols B-I (5-12), were isolated from the Fijian green alga Cladophora socialis and identified by a combination of NMR spectroscopy, mass spectrometric analysis, and computational modeling using DFT calculations. J-resolved spectroscopy and line width reduction by picric acid addition aided in resolving the heavily overlapped aromatic signals. A panel of Gram-positive and Gram-negative pathogens used to evaluate pharmacological potential led to the determination that cladophorol C (6) exhibits potent antibiotic activity selective toward methicillin-resistant Staphylococcus aureus (MRSA) with an MIC of 1.4 μg/mL. Cladophorols B (5) and D-H (7-11) had more modest but also selective antibiotic potency. Activities of cladophorols A-I (4-12) were also assessed against the asexual blood stages of Plasmodium falciparum and revealed cladophorols A (4) and B (5) to have modest activity with EC50 values of 0.7 and 1.9 μg/mL, respectively.
... Gerwick and coworkers (1994) at Oregon State University, Corvalis, Oregon, evaluated over 500 extracts of marine microalgae (primarily cyanobacteria) and macroalgae for their ability to inhibit IMPDH. This assay yielded 24 active extracts and resulted in the isolation of the bromophenolic compound isorawsonol (IC 50 = 18 μM) from the tropical marine green alga Avrainvillea rawsonii (Chen et al. 1994). ...
... The results obtained in this acute inflammation model and the topical efficacy of the extract compared to dexamethasone suggest an interaction with metabolites of the arachidonic acid pathway, mediated mainly by phospholipase A 2 (PLA2) and cyclooxygenase (COX) enzymes (Chen et al., 1994). Thus, the anti-inflammatory mechanism of action of the active components of the extract would involve PLA2. ...
The aim of the present work was to investigate the anti-inflammatory and antinociceptive effects of methanolic extract from D. obtusata using classic models in mice (croton oil-induced ear edema and acetic acid-induced writhing) and a phospholipase A2 activity test. Qualitative analysis of the chemical composition of seaweed was also determined by extraction with solvents of increasing polarity and precipitation and color tests. Results of qualitative chemical study showed the presence of lactonic and phenolic compounds, reduced carbohydrates, other sugars, flavonoids, fatty compounds, triterpenes and steroids. The extract inhibited mouse ear edema in a dose-dependent manner with an efficacy higher than 90% and a mean effective dose of 4.87μg/ear, while intraperitoneal administration presented a moderate activity. The extract did not inhibit phospholipase A2 activity. In the writhing test, the intraperitoneal administration of the extract showed a strong antinociceptive activity (80.2%), while the oral route showed a lower efficacy. In conclusion, this study demonstrated the anti-inflammatory and antinociceptive effects of methanol extract of D. obtusata in experimental models, suggesting its therapeutic potential in the treatment of peripheral painful and/or inflammatory pathologies.
... Bioassyguided fractionation utilizing the inhibitory activity against inosine-5 0 -monophos-phate dehydrogenase inhibitor (IMPDH) leads to isolation of new brominated diphenylmethane derivative. Isorawsonol 30 has been isolated from the tropical green alga Arrainvilla rawsonii by Chen et al. (1994). The activity of IMPDH has been linked with cellular proliferation and inhibition of that enzyme has been demonstrated to have anticancer and immunosuppressive effects . ...
Marine organisms are potentially prolific sources of highly bioactive secondary metabolites that might represent useful leads in the development of new pharmaceutical agents. Algae can be classified into two main groups; first one is the microalgae, which includes blue green algae, dinoflagellates, bacillariophyta (diatoms)… etc., and second one is macroalgae (seaweeds) which includes green, brown and red algae. The microalgae phyla have been recognized to provide chemical and pharmacological novelty and diversity. Moreover, microalgae are considered as the actual producers of some highly bioactive compounds found in marine resources. Red algae are considered as the most important source of many biologically active metabolites in comparison to other algal classes. Seaweeds are used for great number of application by man. The principal use of seaweeds as a source of human food and as a source of gums (phycocollides). Phycocolloides like agar agar, alginic acid and carrageenan are primarily constituents of brown and red algal cell walls and are widely used in industry.
... Avrainvillea cf digitata also showed high cytotoxic and antiproliferative activity against KB cells. This result concurs with previous studies in which Avrainvillea species have been shown to produce isorawsonol, a brominated diphenylmethane derivative, related to the inhibition of cell proliferation (Chen et al. 1994). Additionally, antimitotic glycoglycerolipids play an important role in cell cycle arrest in human cancer cells and have been isolated from this genus (Williams et al. 2007 ), suggesting that Avrainvillea could be used for the isolation of antiproliferatve compounds. ...
Extracts from 27 marine algal species (14 Rhodophyta, 5 Phaeophyta and 8 Chlorophyta) from the Yucatan peninsula (Mexico) were evaluated for cytotoxic and anti-roliferative activity by 3[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays, respectively. In order to determine the specificity of the cytotoxic activity on tumor cells selective index (SI) was also calculated. The following cancer cell lines were employed: normal canine kidney cells (MDCK), human laryngeal carcinoma (Hep-2), human cervix adenocarcinoma (HeLa) and human nasopharynx carcinoma (KB). The results indicated that 44 and 51% of algal species tested showed cytotoxic and anti-roliferative activity, respectively. Most of the cytotoxic extracts were species belong to Chlorophyta, Udotea flabellum and Udotea conglutinate showed the highest cytotoxic activity on all cancer cell lines. For Rhodophyta, the extract of Bryothamnion triquetrum showed an outstanding selective cytotoxicity against Hep-2 cells (CC50 8.29 µg mL−1 with SI=12.04). Two out of five species of Phaeophyta tested (Lobophora variegata and Dictyota caribaea) showed high cytotoxicity activity on KB cell line. The data show that these extracts are potential source of compounds for prevention of certain cancer diseases.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B78.
... Its also causes muscle relaxation and hypothermia when injected into mice (Davies et al., 1984 ). Inosine- 5 -monophosphate dehydrogenase is inhibited by the brominated diphenylmethane derivative, isorawsonol, which has been isolated from Avrainvillea rawsonii (Chen et al., 1994). The linear diterpenes eleganolone and elegandiol, isolated from Cystoseira brachycarpa var. ...
In the last three decades the discovery of metabolites with biological activities from macroalgae has increased significantly. However, despite the intense research effort by academic and corporate institutions, very few products with real potential have been identified or developed. Based on Silverplatter MEDLINE and Aquatic Biology, Aquaculture & Fisheries Resources databases, the literature was searched for natural products from marine macroalgae in the Rhodophyta, Phaeophyta and Chlorophyta with biological and pharmacological activity. Substances that currently receive most attention from pharmaceutical companies for use in drug development, or from researchers in the field of medicine-related research include: sulphated polysaccharides as antiviral substances, halogenated furanones from Delisea pulchra as antifouling compounds, and kahalalide F from a species of Bryopsis as a possible treatment of lung cancer, tumours and AIDS. Other substances such as macroalgal lectins, fucoidans, kainoids and aplysiatoxins are routinely used in biomedical research and a multitude of other substances have known biological activities. The potential pharmaceutical, medicinal and research applications of these compounds are discussed.
... Other bioactive secondary metabolites have been isolated from Avrainvillea spp. but their role in plant-herbivore interactions is unknown (Colon et al., 1987;Chen et al., 1994) 31 Gillespie et al. (1985a) Boodlea Green filamentous turf alga with a spongy thallus (Littler and Littler, 2000). Little data available on palatability although it is consumed to some extent by certain crabs (Sato and Wada, 2000) 10-78 Kaly and Jones (1994) ...
The benthic dinoflagellate Gambierdiscus toxicus produces polyether toxins that cause ciguatera fish poisoning in humans. The toxins initially enter food webs when fish forage on macroalgae, or other substrates, hosting this epiphytic dinoflagellate. Population studies of G. toxicus and risk assessments in ciguatera-prone regions often rely on quantifying dinoflagellates on macroalgae. Underlying these studies is the assumption that the algae sampled represent a readily consumable resource equally available for benthic grazers. However, many algal hosts of G. toxicus possess a variety of defenses against grazing, and host–dinoflagellate associations may act as toxin sources or sinks depending on their palatability. Marine macroalgae may tolerate or avoid herbivory by exhibiting fast growth, by having poor nutritional quality, by utilizing spatial or temporal escapes or by using chemical or structural defenses. Thus, rapidly consumed algae that cope with herbivores by growing fast, such as many filamentous turfs, could be responsible for a high toxin flux even at low dinoflagellate densities. In contrast, ubiquitous unpalatable algae with much higher dinoflagellate densities might contribute little to toxin flux, and effectively act as refuges for G. toxicus. To date, G. toxicus has been reported from 56 algal genera, two cyanobacteria, one diatom, and one seagrass; 63% of these contain species that are defended from fish grazing and other grazers via chemical, morphological or structural defenses, by low nutritional quality, or by a combination of defensive strategies. High dinoflagellate densities on unpalatable macroalgae could indicate passive accumulation of cells on undisturbed hosts, rather than population explosions or active toxin sources for food webs. Understanding the flow of ciguatoxins in nature requires consideration of the ecology of both G. toxicus and its algal hosts. The complexity of marine algal–herbivore interactions also has consequences for other benthic dinoflagellates that produce toxins, which accumulate in consumers.
... BPs share one or several benzene rings, a varying degree of bromine and hydroxyl-substituents (see schemes). The first two marine BPs were isolated from the red algae Rhodomela larix [4] and thereafter, many novel BPs were isolated and identified from diverse species of marine algae, including red algae , brown algae [34][35][36][37][38][39], and green algae [40][41][42][43][44][45][46][47][48]. It seems that species collected at low tide have a higher content of simple BPs [49]. ...
Marine algae contain various bromophenols that have been shown to possess a variety of biological activities, including antioxidant, antimicrobial, anticancer, anti-diabetic, and anti-thrombotic effects. Here, we briefly review the recent progress of these marine algal biomaterials, with respect to structure, bioactivities, and their potential application as pharmaceuticals.
Marine algae are the source of a plethora of halogenated compounds, in particular brominated phenols, possessing various bioactivities. Since these natural products are typically unavailable commercially, isolation is usually indispensable for biological activity testing. However, targeted isolation may be challenging due to difficulties in identifying desired compounds via high-resolution LC–MS in crude extracts or fractions. While bromophenols have been extensively reviewed regarding their bioactivities, less attention has been given to their distribution and chemotaxonomic relevance among marine algae. Knowledge of the distribution of bromophenols may aid species identification and also point to species containing potentially novel compounds. To facilitate targeted and untargeted isolation of bromophenols from marine algae, an overview of the distribution and chemotaxonomic relevance of algal bromophenols considering recent phylogenetic findings is presented along with key analytical features of bromophenols relevant for mass spectrometric identification. Additionally, a comprehensive database listing brominated phenols from marine algae and their key analytical properties has been constructed.
Macroalgae are the source of many harmful allelopathic compounds, which are synthesized as a defense strategy against competitors and herbivores. Therefore, it can be predicted that certain species reduce aquaculture performance. Herein, the allelopathic ability of 123 different taxa of green, red, and brown algae have been summarized based on literature reports. Research on macroalgae and their allelopathic effects on other animal organisms was conducted primarily in Australia, Mexico, and the United States. Nevertheless, there are also several scientific reports in this field from South America and Asia; the study areas in the latter continents coincide with areas where aquaculture is highly developed and widely practiced. Therefore, the allelopathic activity of macroalgae on coexisting animals is an issue that is worth careful investigation. In this work, we characterize the distribution of allelopathic macroalgae and compare them with aquaculture locations, describe the methods for the study of macroalgal allelopathy, present the taxonomic position of allelopathic macroalgae and their impact on coexisting aquatic competitors (Cnidaria) and herbivores (Annelida, Echinodermata, Arthropoda, Mollusca, and Chordata), and compile information on allelopathic compounds produced by different macroalgae species. This work gathers the current knowledge on the phenomenon of macroalgal allelopathy and their allelochemicals affecting aquatic animal (competitors and predators) worldwide and it provides future research directions for this topic.
From the green alga Avrainvillea amadelpha, two new naturally halo-benzaldehyde derivatives were isolated by various chromatographic methods along with 10 known metabolites of bromophenols, sulfonoglycolipid, and steroids. Based on the 1D and 2D NMR spectra as well as on MS data, the structures of the new compounds were identified as 5-bromo-2-(3-bromo-4-hydroxybenzyl)-3,4-dihydroxybenzaldehyde named avrainvilleal (1), and 3-iodo-4-hydroxy-benzaldehyde (2). Using SRB assay, both compounds showed mild and weak cytotoxic activity against HeLa and MCF-7 cancer cell lines, compared to the good activity of their extract (IC50 values 3.1 and 4.3 μg/mL, respectively). However, avrainvilleal (1) displayed an effective scavenged DPPH radical activity with IC50 value 3.5 μM, compared to the antioxidant quercetin with IC50 value 1.5 μM.
Modern scientific advancements and research on marine microbes has revealed their significance as producers of therapeutic products useful in treating various human diseases. Microbes in marine habitat have evolved to adapt to the harsh condition that prevails in the ocean. Their struggle to compete for space and nutrients has paved way for the synthesis of different novel enzymes possessing distinctive characteristics. Thus, marine habitat hosts many remarkable microorganisms that offer unique biologically active compounds, enzymes endowed with astonishing properties, and mechanism to survive in extreme environmental conditions. The utilization of marine biotic resources grows at an extraordinary growth rate of 12% per annum and is evident from about 4900 patents filed connected with marine genetic resources and 18,000 natural compounds. This concern has boosted research all over the world to explore the untapped potential hidden in marine microbes, which has lot of biotechnological applications that includes bioactive compounds (metabolites) for therapeutics, novel enzymes, cosmetics, and nutraceuticals. This book chapter will meticulously deliberate the utilization of marine resources by biotechnological applications for therapeutics like antibiotics, chemical compounds, biopolymer, enzymes, and various microbial biomedical purposes such as drug delivery and tissue engineering from marine biota (bacteria, fungi, and algae).
Marine organisms, especially the marine algae, contain various bromophenol compounds that have been shown to possess a variety of biological activities, mainly including antioxidant, antimicrobial, anticancer, anti‐diabetic effects and so on. Here, we briefly review the recent progress of these emerging marine biomaterials, with respect to structures, bioactivities and their potential application as pharmaceuticals. The problem and prospect in developing BPs as novel agents used clinically are also presented.
Marine plants such as algae (blue-green algae and seaweeds), seagrasses, mangrove plants, salt-tolerant or salt-loving plants (halophytes) and coastal sand dune plants are known to generate approximately 70% of oxygen on earth, and help regulate oxygen in the atmosphere. These plants are potential sources of nutrients and are also considered valuable for the development of new drugs owing to their unique bioactive compounds. This book provides the taxonomy, common name, global distribution, habitat, diagnostic features and pharmaceutical compounds (along with their activities) of 400 species of marine plants, accompanied by high quality illustrations.
Biology and Ecology of Pharmaceutical Marine Plants is the first comprehensive book of its kind written by scientists from both the Marine Biology and Pharmacy disciplines to fill the long-felt need for a marine natural products book devoted exclusively to plants. It should be a standard reference for students, researchers and teachers of disciplines such as Pharmacy, Fisheries Science, Marine Biology, Life Sciences, Biotechnology and Biochemistry, as well as a valuable guide for pharmaceutical companies involved in the development of new drugs from marine plants.
Cyanobacterium samples were collected from fresh water of Tokat city in Turkey, and then isolation and cultivation of Chroococcus minutus were achieved successfully. TLC (Thin layer chromatography) and HPLC (High Performance Liquid Chromatography) analyses revealed that the C. minutus consisted of norharmane as a major product. So amount of norharmane was determined during the growth process. Growth and norharmane production of C. minutus were executed under salt stress and pH stress conditions. The most growth and the highest production of norharmane were detected at 16th day. Therefore inoculation process was performed at 16th day. Salt stress was evaluated at 0.5, 1.0, 3.0 and 5.0 M concentrations. The most norharmane was synthesized by C. minutus at 5 M concentration. The norharmane production and the growth were higher at pH 9 than that of the pH 5. Most norharmane was produced at pH 7.
The recent literature (1992 - early 1996) on secondary metabolites from marine algae has been reviewed and selected results concerning more than one hundred bioactive compounds are reported. The review is specifically devoted to the seaweeds (Chlorophyta, Phaeophyta and Rhodophyta) and does not include metabolites from microalgae and Cyanobacteria (blue-green algae). Emphasis has been placed on novel compounds, but some recent reports about previously known bioactive metabolites have also been reviewed.
A variety of bioactive metabolites has recently been obtained from marine algae, including terpenoids (among them the halogenated mono- and sesquiterpenoids typically produced by red algae), compounds of mixed biogenesis and further miscellaneous compounds. The reported activities range from properties of pharmacological interest, i.e. cytotoxicity against tumoral cultured cells, antimicrobial activity, antiviral activity, etc., to other activites of ecological or agronomical significance, such as antifeedant activity against marine predators or insecticidal activity.
The review of the recent literature on secondary metabolites from marine algae indicates that the search for new bioactive metabolites from seaweeds is an active sector of the chemistry of natural products, stimulating the application of sophisticated physical techniques like two dimensional NMR as well as intriguing syntheses of compounds of biomedical interest.
Cancer is one of the most dreadful human diseases and it has a multiple etiology, including lifestyle, culture and environment. Despite there being many synthetic anticancer drugs available in the market, there remains a need for potent drugs of natural origin. In this regard, marine algae, which are rich in phytochemicals and show a wide species diversity, are a promising source. Information is available on the health benefits of marine algae as both preventive and curative agents for ailments. However, marine algae-derived compounds have not as yet entered post-clinical trials. The present review consolidates the available information on marine algae-derived anticancer principles and their possible mode of action.
This chapter reviews the major metabolic themes that are characteristic of the prominent groups of marine algae and cyanobacteria. The taxonomic organization of the chapter facilitates an appreciation of the uniqueness of each of these groups in their capacity to elaborate specific classes of secondary metabolites. For each compound discussed, which are chosen as representatives of chemical themes, a brief story is presented which describes the natural history of the organism, the isolation of the natural product, its structure elucidation, and as appropriate, the pharmacology, chemical ecology, and biosynthesis of the isolated metabolite. Many unanswered questions remain in understanding these diverse algal chemistries, and numerous areas for future exploration are suggested throughout the chapter.
The article contains sections titled:Whittaker's Five Kingdoms System (1959)Discovery of Archaea: Ternary Model of Living Organisms (Woese and Fox, 1977)Characteristics of Cell MembranesSome Recent Data on TerpenesMain Stages of EvolutionExceptional Resources of Marine BiodiversityKeywords:taxonomic system;chemotaxonomy;classification system;Archaea (Archaebacteria);chemotaxonomy;classification systems;DXP/MEP pathway;Eukaryotes;evolution;LUCA;marine biodiversity;membrane phospholipids;MVA pathway;Prokaryotes;taxonomic systems
A family of diphenylmethane derivatives has been synthesized and their luminescence properties characterized. While in solution the compounds are weakly emissive, showing no aggregation-induced emission enhancement, the crystals of three dialkyl 5,5'-methylenebis(2-hydroxybenzoate) samples exhibit intense emission. This emission enhancement upon crystallization is ascribed to particular molecular packing, which stiffens the structure of the compounds via hydrogen bonds, preventing consecutive pi-pi interactions.
Inhibitory potencies against alpha-glucosidase activities were compared among bromophenols obtained from extracts of three Rhodomelaceae red algae, Symphyocladia latiuscula, Odonthalia corymbifera, and Polysiphonia morrowii. The bromophenols from these species are characterized by a number of Pr atoms per benzene ring: S. latiuscula, three Br atoms (1 and 2); O. corymbifera, two Br atoms (3-7); and P. morrowii, one Br atom (8 and 9). The bromophenols exhibited mixed inhibition against yeast alpha-glucosidase reaction. In particular, symmetric dibenzyl ethers, bis(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (2) and bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), exhibited about 10(3) fold smaller K-i values than the other bromophenols. Their inhibition modes are disclosed to be mixed inhibition closed to competitive inhibition. Inhibitory potencies of the bromophenols increased with the increasing degree of bromo-substitution per benzene ring and the decreasing degree of methyl-substitution. In contrast to the strong inhibitory activity against yeast alpha-glucosidase activity, the bromophenols moderately inhibited rat-intestinal sucrase and maltase activity. The inhibitory potencies were all comparative among the bromophenols examined.
During the biological evolution, marine macroalgae have developed biochemicals tools in order to utilize components of seawater such as sulfates and halogens, to produce a variety of chemicals (secondary metabolites). This review shows and discuss the occurrence of sulfated and/or halogenated phenolic compounds in seaweeds.
As defined in the broadest sense, algae are oxygen-generating, photosynthetic organisms other than embryophyte land plants and lichens (Cavalier-Smith, T. 2007. Evolution and relationships of algae: major branches of the tree of life. In Unravelling the algae: the past, present and future of algal systematics, eds. Brodie, J. and Lewis J, pp. 21–55. CRC Press. The Systematics Association Special Volume 75). They are an artificial and highly heterogeneous aggregation of organisms belonging to many different evolutionary lineages, and therefore highly diverse from a genetic point of view. This genetic diversity is reflected in the huge diversity exhibited by algae in terms of morphological, ultrastructural, ecological, biochemical, and physiological traits.
The chemistry and bioactivity of metabolites produced by some Codiacean plants (Species of the genera: Avrainvillea; Chlorodesmis; Codium; Ilalimeda; Penicillus; Rhipocephalus and Tydemania and Udotea) have been reviewed. The metabolites isolated include halogenated compounds, terpenoids, oxygenated sterols, sulphated polysaccharides, proteoglycans and lectins; bioactivities such as antiviral (including anti-HIV), antibacterial, antifungal, ichthyotoxic, cytotoxic, antitumor, blood anticoagulant etc. have been reported.
A novel brominated and chlorinated compound, C10H6N2Br4Cl2, bioaccumulating in seabird eggs was identified and characterized by low- and high-resolution electron impact ionization (EI), electron capture negative ionization (ECNI), and ammonia positive chemical ionization (PCI) mass spectrometry. This compound is the major congener of a series of four hexahalogenated species. The major congener was determined in egg samples from Leach's storm-petrel, rhinoceros auklet, glaucous-winged gull, and black-footed albatross from the Pacific coast area; Leach's storm-petrel, Atlantic puffin, and herring gull from the Atlantic coast; and herring gull from the Great Lakes using GC-ECNI-MS. The concentrations of C10H6N2Br4Cl2 in the Pacific Ocean samples ranged from 1.8 to 140 ng/g (wet weight), and were significantly higher than the Atlantic Ocean samples (p = 0.037). The Pacific Ocean samples contained levels of C10H6N2Br4Cl2 approximately 1.5−2.5 times higher than in the Atlantic Ocean samples of the same or ecologically similar species. The compound was not detected in any of the samples from the Great Lakes. The Pacific Ocean offshore surface feeders had the highest concentrations (34−140 ng/g) when compared to the other samples (0.61−5.6 ng/g). Its strictly marine occurrence and relatively high nitrogen content indicate that C10H6N2Br4Cl2 probably is a marine natural product, found at highest concentrations in the Pacific Ocean surface feeding birds. A possible structure of C10H6N2Br4Cl2 is 1,1‘-dimethyl-tetrabromodichloro-2,2‘-bipyrrole.
Overview of IMPDH Kinetic Mechanism and Substrate Interactions Chemical Mechanism Protein Conformational Flexibility and Mechanism of Water Activation Species-Specific Drug Selectivity Monovalent Cation Activation Subdomain Conclusions Acknowledgments References
Extracts and pure compounds isolated from four samples of Dysidea sp. sponges collected from two geographically distinct regions of the Indo-Pacific (Chuuk Atoll and Fiji) were assayed against five different enzyme assays, four of which are relevant to anticancer drug discovery and one of which (15-lipoxygenase) may detect compounds significant in modulating the development of atherosclerotic plaque. The pure compounds that inhibited various enzymes were polybrominated phenols and polybrominated phenoxyphenols. Fourteen of these phenols were isolated, six of which were new compounds. A variety of the phenols inhibited inosine monophosphate dehydrogenase (IMPDH), guanosine monophosphate synthetase, and 15-lipoxygenase. No activity was observed with protein tyrosine kinase pp60v-src or matrix metalloprotease.
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Fractionation of the organic extract obtained from the Dominican green alga Avrainvillea nigricans led to the isolation of avrainvilloside (2), a new glycoglycerolipid bearing the extremely rare 6-deoxy-6-aminoglucose moiety. The structure of avrainvilloside has been established on the basis of spectroscopic data and methanolysis/GC-MS analysis.
Nine new gentisyl alcohol derivatives, namely, the trimeric terrestrol A (8), dimeric terrestrols B-H (1-7), and a monomeric derivative (12), together with four known analogues (9-11, 13) were isolated from the marine-derived fungus Penicillium terrestre. The structures of the new compounds were elucidated by spectroscopic methods including one- and two-dimensional NMR as well as low- and high-resolution mass spectrometric analysis. These new compounds (1-8, 12) showed cytotoxic effects on HL-60, MOLT-4, BEL-7402, and A-549 cell lines with IC50 values in the range 5-65 microM. Compound 6 also showed moderate inhibitory activity against protein tyrosine kinases (Src and KDR). Furthermore, all new compounds exhibited moderate radical scavenging activity against DPPH with IC50 values in the range 2.6-8.5 microM.
A novel brominated diphenyl methane derivative, rawsonol, has been isolated from the green alga Avrainvillea rawsoni, and its structure determined by chemical and spectral methods. Rawsonol which is a methyl ether formed via condensation/methylation of two molecules of the known metabolite avrainvilleol, inhibited the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.
A new brominated diphenylmethane derivative, avrainvilleol, has been isolated from the green alga Avrainvillea longicaulis, and its structure determined by chemical and spectral methods. Avrainvilleol was toxic toward reef fishes at 10 μg/ml levels, showed antibacterial activity and at 800 ppm induced significant feeding deterrence in the tropical damselfish Pomacentrus coeruleus.
A rapid microassay method for the accurate measurement of the activity of inosine 5'-monophosphate dehydrogenase in crude tissue extracts was described. [8-14C]IMP and the radioactive products were separated by high-voltage electrophoresis in 0.1 M potassium phosphate buffer, pH 7.0, for 45 min. This separation method provides an analysis of the possible interfering reactions such as the metabolic conversion of the substrate IMP to inosine and adenylosuccinate, and the loss of the product XMP to xanthosine or GMP and to other metabolites. Low blank values were consistently obtained with this method because the XMP spot moves faster than the IMP spot. The major advantages of this assay method are direct measurement of IMP dehydrogenase activity in crude extracts, high sensitivity (with a limit of detection of 5 pmol of XMP production), high reproducibility (less than +/- 3.6%), low blank values (60-80 cpm), speed (2 h per 30 assays), and capability to measure activity in small amounts of tissue (10-50 mg wet wt).
A new brominated diphenylmethane, 5'-hydroxyisoavrainvilleol, was isolated from the tropical green macrophyte, Avrainvillea nigricans, using conventional chromatographic techniques. The structure is based on a combination of spectrochemical arguments, including a detailed analysis of the long range 1H-13C coupling constants. The natural product shows gram-positive antimicrobial activity.