Synthesis of new bioisosteric hemiasterlin analogues with extremely high cytotoxicity

Abstract

International audienceIn this article, we report a convenient and efficient method for the synthesis of new simplified derivativesof hemiasterlin in which the α,α-dimethylbenzylic moiety A is replaced by α,β-unsaturated aryl groupsas Michael acceptor. Most of these derivatives have a strong cytotoxic activity on three human tumorcell lines (KB, Hep-G2 and MCF7). Analogs 17b and 17f showed a high cytotoxicity against KB andHep-G2 cancer cell lines comparable to paclitaxel and ellipticine