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.
Chinh Pham The  1 ,  Tuyet Anh Dang Thi  1 ,  Thi Phuong Hoang  1 ,  Quoc Anh Ngo  1 ,  Duy Tien Doan  1 ,  Thu Ha Nguyen Thi  1 ,  Tham Pham Thi  1 ,  Thu Ha Vu Thi  1 ,  M Jean  2 ,  P van de Weghe  3 ,  Tuyen Nguyen Van  1
Affiliations
  • 1. Institute of Chemistry-Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam.
  • 2. Equipe Produits Naturels, Synthèses et Chimie Médicinale (PNSCM), UMR CNRS 6226-Institut des Sciences Chimiques de Rennes, Université de Rennes 1, UFR Sciences Pharmaceutiques et Biologique, 2, Avenue du Prof L. Bernard, F-35043 Rennes Cedex, France.
  • 3. Equipe Produits Naturels, Synthèses et Chimie Médicinale (PNSCM), UMR CNRS 6226-Institut des Sciences Chimiques de Rennes, Université de Rennes 1, UFR Sciences Pharmaceutiques et Biologique, 2, Avenue du Prof L. Bernard, F-35043 Rennes Cedex, France. Electronic address: [email protected].
PMID: 24745968 DOI: 10.1016/j.bmcl.2014.03.091
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.