Synthesis and Antimitotic/Cytotoxic Activity of Hemiasterlin Analogues
- 31 December 2002
- journal article
- Published by American Chemical Society (ACS) in Journal of Natural Products
- Vol. 66 (2) , 183-199
- https://doi.org/10.1021/np020375t
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.Keywords
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