Tunicates active metabolites

The in vivo antitumour activity of extracts of the tunicate Ecteinascidia turbinata was noted in the late 1960s [152] but the active metabolites were only isolated and identified much later by two research groups. These complex alkaloids were termed the ecteinascidins and are... 

The didemnolines A-D (30-33) isolated from the tunicate Didemnum sp. represent an additional family of P-carboline metabolites [33]. They differ from the other derived P-carboline compounds in that they are substituted at the N9 position rather than at the C-l position. All of these compounds showed moderate cytotoxic activity against KB cells, with the sulfoxide-containing compound, didemnoline C (32), being the most active with an IC50 value of 0.28 pg/ml. Compounds 30 and 32 also exhibited... 

Since the discovery of amphimedine by Schmitz and co-workers in 1983 [36], the polycyclic alkaloids based on the pyrido[, /]acridine skeleton have emerged as a well-defined class of marine metabolites, with significant biological activities, isolated from sponges and tunicates [37]. The less common group of sulfide pyridoacridines were only obtained from tunicates and they include the shermilamines, the varamines-lissoclins-diplamine group, and tintamine, another polycyclic alkaloid closely related to them. 

Unlike carbazoles, haiogenated (3-carbolines are abundant in nature [1[. For example, the simple eudistomin O (7-bromo-(3-carboline) (40) is a ubiquitous marine ascidian metabolite [44[. Indeed, the tunicate genus Eudistoma has furnished most of the extant haiogenated (3-carbolines, some of which have significant antiviral (polio, herpes) and microbial activity. The Caribbean Eudistoma olivaceum produces at least 15 brominated carbolines [1[. A study of Eudistoma gilboverde uncovered the new eudistomins 41-43[45[, and the Australian ascidian Pseudodistoma aureum has... 

Three new oxepin-containing natural products oxepinamides A-C 166-168 and two new fumiquinazoline metabolites fumiquinazolines H-I 169-170 were isolated from organic extracts of the culture broth and mycelia of Acremonium sp., a fungus obtained from the surface of the Caribbean tunicate Ecteinascidia turbinata Compound 166 exhibited good anti-inflammatory activity in a topical RTX-induced mouse ear edema assay. Compounds 169 and 170 both exhibited weak anti-fungal activity towards Candida albicans in a broth microdilution assay. Total... 

The ecteinascidins (66-69) are a family of tetrahydroisoquinoline alkaloids present in trace quantities in the tunicate Ecteinascidia turbinata [119 - 123]. These metabolites exhibit potent activity against various tumor models in mice and have recently entered clinical trials [123]. 

Tunicates (ascidians) are an excellent source of novel biologically active compounds of varied biosynthetic origin, particularly nitrogen-containing amino-acid-derived metabolites [146], The most important compounds discovered to date from tunicates may be the didemnins, potent cytotoxic and antiviral cyclic... 

Much interest and research over the past 15 or so years has been directed towards ascidian metabolites because of the high incidence of pharmacological activity that they display. Few comprehensive reviews exist on the topic the only general ones being those produced by Davidson in 1993 [1,2] and the Marine Natural Product literature reviews by Faulkner which always contain a section on tunicate metabolites [3-13]. Although a number of non-nitrogenous metabolites have been isolated from the tunicates, the majority of compoimds isolated have been derived from amino acids. In particular, the two most commonly encountered classes are cyclic peptides and polycyclic aromatic alkaloids. 

A number of metabolites which appear to be derived from Tyrosine, Dopa, or Topa residues and to have similar biogenetic origins to the tunichromes have been reported. Rigidin (48), isolated from the Okinawan marine tunicate Eudistoma c.f. rigida exhibited calmodulin antagonistic activity with an IC50 of 5 x lO M against calmodulin-activated brain phosphodiesterase [42]. Some other pyrrolo[2,3d]pyrimidine-2,4-diones which have been synthesised have shown weak affinity for the benzodiazepine receptor. 

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