Metabolite didemnin

Most of the highly bioactive marine metabolites are also highly toxic, which is very serious. If enough materials are available, parent compounds could be modified to reduce their toxicity or to improve their therapeutic efficacy. However, such attempts have not been accomplished because of limited amounts of materials and their highly complex structures, except for readily synthesized substances such as didemnins and dolastatins. 

Importantly, Lindquist et al.53 also document that ascidians can exhibit chemical differences between defensive secondary metabolites among adults and larvae. For example, larvae from colonies of Sigillina cf. signifera contained more tambjamine C, less tambjamine E, and no tambjamine F as compared to adults.65 Moreover, larvae of Trididemnum solidum contain only four of the six didemnins found in adults.53 This could be the result of different selective pressures during planktonic vs. benthic life history phases. In contrast, Lucas et al.44 found no differences in the saponin chemical defenses of the embryos, larvae, and adults of the sea star Acanthaster planci. Clearly, additional studies are needed to expand the evaluation of ontogenetic shifts in defensive chemistry in marine organisms. 

The Caribbean tunicate Trididemnum solidum and its larvae contain a complex mixture of didemnin/ nordidemnin metabolites that act as feeding deterrents in field-based assays at below natural concentrations. The most potent metabolite is nordidemnin B 147.28 Crude extract mixtures enriched in didemnin B 148 induce vomiting in the spotted pinfish L. rhomboides, causing these fish to avoid feeding.173 The larvae of other didemnid ascidians are also protected by the presence of deterrent chemicals.28 174... 

It has been amply demonstrated that ascidians are prolific producers of novel bioactive secondary metabolites [64-66]. A significant number of ascidian-derived compounds have entered into preclinical trials as antitumor agents [67]. Examples include didemnin B (went through phase... 

The tunicates have been the focus of many investigations due to the biomedical potential of such metabolites as the didemnins, [118] ecteinascidins, [119 - 123] and the eudistomins [124], While the biosynthesis of the didemnins has not been investigated, the metabolic origin of the latter two families of compounds has been examined. The eudistomins are (3-carboline alkaloids produced by the tunicate Eudistoma... 

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... 

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