Isolation and structure of the human cancer cell growth inhibitory cyclic decapeptides phakellistatins 7, 8 and 91,2

Bioorganic & Medicinal Chemistry Letters
1995.0

Abstract

Phakellistatins 7-9 respresent the first cancer cell growth inhibitory (P388 ED50 3.0, 2.9 and 4.1 Ixg/mL respectively) cyclic decapeptides. Each was isolated from the Federated States of Micronesia (Chunk) marine sponge Phakellia costata. Animals, plants and microorganisms constitute a vast reservoir of peptides with potentially important medicinal properties that range from the partially understood higher animal hormones to the lower organism peptides of generally unknown natural function. Among the latter categories are the diverse series of marine shell-less mollusc antineoplastic 35 and cytotoxic 6-7 dolastatins, the cytotoxic marine ascidian peptides, s the Australian frog antimicrobal and antiviral coerin-type cyclic peptides, 9 higher plant (Aster tatoricus, Compositae) antineoplastic cyclic pentapeptides, l° fungal antibioticsll and the streptomyces antineoplastic antibiotic himastatin. 12 Clearly, discovery and biological evaluation of such valuable naturally occurring peptides is only in a very early phase. 13 We herein report discovery of the first three cancer cell growth inhibitory cyclic decapeptides designated phakellistatins 7, 8 and 9 from a marine sponge and to our knowledge from any marine animal.

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