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Synthesis and antimitotic/cytotoxic activity of hemiasterlin analogues

TitleSynthesis and antimitotic/cytotoxic activity of hemiasterlin analogues
Publication TypeJournal Article
Year of Publication2003
AuthorsNieman, JA, Coleman, JE, Wallace, DJ, Piers, E, Lim, LY, Roberge, M, Andersen, RJ
JournalJournal of Natural Products
Volume66
Pagination183-199
Date PublishedFeb
Type of ArticleArticle
ISBN Number0163-3864
Keywords(-)-HEMIASTERLIN, AGENTS, ALPHA-AMINO-ACIDS, ASYMMETRIC-SYNTHESIS, AZIDATION, CYTOTOXIC PEPTIDES, ELEUTHEROBIN, TRIPEPTIDE, TUBULIN
Abstract

The antimitotic sponge tripeptide hemiasterlin (1) and a number of structural analogues have been synthesized and evaluated in cell-based assays for both cytotoxic and antimitotic activity in order to explore the SAR for this promising anticancer drug lead. One synthetic analogue, SPA110 (8), showed more potent in vitro cytotoxicty and antimitotic activity than the natural product hemiasterlin (1), and consequently it has been subjected to thorough preclinical evaluation and targeted for clinical evaluation. The details of the synthesis of hemiasterlin (1) and the analogues and a discussion of how their biological activities vary with their structures are presented in this paper.

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