Bioactive metabolites invertebrates

There are several approaches that can be taken to supply material for pharmaceutical evaluation. Two of these, invertebrate cell culture and fermentation of associated microorganisms, begin with determining the biogenetic origin of the compound. There are numerous reports of metabolite localization, primarily in sponges, in which production of a bioactive metabolite has been inferred or demonstrated to be localized either in a host invertebrate cell or in microbial associates which include cyanobacteria and heterotrophic bacteria and fungi.72-73... 

Isolation and culture of putative symbiotic microorganisms to obtain the bioactive metabolites isolated from the invertebrate-microbe assemblages has been particularly problematic. It has been estimated that only 1% of marine microbes can be isolated and fermented using techniques modified to approximate marine conditions. However, to address this problem, several groups have used differential fractionation or flow cytometric techniques to separate populations of extracellularly associated microorganisms from invertebrate host cells. Chromatographic and spectroscopic analyses of the enriched cell fractions have been used to determine which cell type is producing the compounds. The assumption is that the metabolites are produced in the cell types in which they are detected. 

Oceans provide enormous and diverse habitats for marine life. The distinct feature of marine life is the domination of invertebrates, which account for more than 95% of marine animals. Most marine invertebrates are sessile and soft-bodied and lack obvious physical defenses. Instead, they have evolved to defend by chemical means against predation and overgrowth by other fouling organisms. In fact, their secondary metabolites have unusual structural features and potent biologic activities, many of which are not found in terrestrial natural products. This review focuses on bioactive metabolites isolated mainly from marine invertebrates with a special emphasis on the uniqueness of marine natural products. 

The world s oceans cover more than 70% of the earth s surface and represent greater than 95% of the biosphere. Species ranging from 3 to 100 million are estimated to inhabit in the oceans. All but 1 of the 35 principal phyla in the animal kingdom are represented in aquatic environments 8 phyla are exclusively aquatic. Most of them are sessile and soft-bodied organisms, most of which have evolved by chemical means to defend against predators and overgrowth by competing species. As expected, a variety of bioactive metabolites were found in marine invertebrates (see a series of reviews on marine natural products pubbshed in Natural Product Reports since 1984). 

There have been no natural products investigations of soft corals from the cool temperate west coast of southern Africa. Soft corals are common along the south-east coast of South Africa and as part of our ongoing search for bioactive metabolites from the marine invertebrate fauna of the Tsitsikamma Marine Reserve we isolated four bioactive xenicane diterpenes, the tsitsixenicins A - D (93 - 96) from the endemic soft coral Capnella thyrsoidea (Family Nephtheidae) [91]. The structures of 93 -96 were delineated from standard analysis of their NMR data and comparison of these data with those published for related compounds e.g. 9-deacetoxy-14,15-deepoxyxeniculin (diastereomic with 93) isolated from the Red Sea soft coral Xenia macrospiculata [92]. 

In addition, as part of a continuing study of bioactive metabolites from aquatic invertebrates we recently investigated the chemistry and biological activity of the solvent extracts of an unidentified Pseudoptergorgia specie collected from Indonesia [8]. We describe our findings under the genus americana. 

Mendola, D. (2003) Aquaculture of three phyla of marine invertebrates to yield bioactive metabolites process developments and economics. Biorrtol. Eng., 20, 441-458. 

In the search for bioactive marine secondary metabolites, drugs or drug leads with new modes of action, many invertebrates with new modes of action have been explored and tested in a variety of assays. Many marine natural products were found to be cytotoxic to an assortment of tumor cells, Some parts of the marine natural products were also found to be ichthyotoxic so as to defend themselves. Two examples, out of many, are the latrunculins and sarcophine. ... 

In spite of the difficulties reported, model primary culture systems have been established for shallow-water sponges that produce bioactive secondary metabolites. It has been demonstrated that cultured cells can be stimulated to divide by mitogens and retain the ability to synthesize bioactive compounds.115116 These successes suggest that, with a greater understanding of requirements for growth and compound production, invertebrate cell culture may become a viable source for bioactive marine natural products. 

Targett NM, Ward JE (1991) Bioactive microalgal metabolites mediation of subtle ecological interactions in phytophagous suspension-feeding marine invertebrates. Bioorganic Mar Chem 4 91-118... 

This review describes bioactive compounds isolated from marine algae and invertebrates with an emphasis on then-uniqueness. Because of limited space, metabolites from bacteria, cyanobacteria, and fungi cannot be included, although some from cyanobacterial and endosymbiotic bacterial origins are described (some reviews on metabolites of marine bacteria, cyanobacteria, and fungi are provided in the Further Reading section). Structures and bioactivities are described for compounds that represent natural product classes, but steroids and carotenoids are not included. 

ABSTRACT Marine invertebrates such as ascidians, sponges and others are a prolific source of bioactive secondary metabolites. We have isolated a variety of marine natural products from the Okinawan marine invertebrates by using the sea urchin egg assay. Our recent work, the isolation, structure determination and activities of chlorinated macrolides, sesterterpenic acids, a bromotyrosine derivative, acetogenin derived endoperoxides, diterpene alkaloids, sesquiterpene quinones and spiro-sesquiterpenes, is presented in this article. The syntheses of these metabolites are also described. 

In this chapter, a rationale of the structure-activity relationships of various series of bioactive secondary metabolites from Indo-Pacific marine invertebrates is reviewed. These include alkaloids, terpenes and polybrominated diphenyl ethers which were subjected to a series of bioassays in search for insecticidal, antibacterial, fungicidal, and cytotoxic lead compounds. From these various biotests, it was observed that the bioactivity of an analogue is not due to general toxicity but rather possesses a degree of specificity on a particular target biomolecule. The relationship between chemical structures and biological activity is related to the specific action of a compound. 

Table 5. Bioactivity of Metabolites Isolated from Indo-Pacific Marine Invertebrates...

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