Synthesis of new simplified hemiasterlin derivatives with α,β-unsaturated carbonyl moiety

Bioorg Med Chem Lett. 2014 May 15;24(10):2244-6. doi: 10.1016/j.bmcl.2014.03.091. Epub 2014 Apr 5.

Abstract

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

Keywords: Cytotoxicity; Hemiasterlin; Tripeptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • KB Cells
  • MCF-7 Cells
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Structure-Activity Relationship

Substances

  • Oligopeptides
  • hemiasterlin