Synthesis of new bioisosteric hemiasterlin analogues with extremely high cytotoxicity

  • Bioorg Med Chem Lett. 2014 Nov 15;24(22):5216-8. doi: 10.1016/j.bmcl.2014.09.065.
Thi Tuyet Anh Dang  1 ,  The Chinh Pham  1 ,  Quoc Anh Ngo  1 ,  Thi Thu Ha Vu  1 ,  Tien Dung Nguyen  1 ,  Duy Tien Doan  1 ,  Thi Cham Ba  1 ,  M Jean  2 ,  P van de Weghe  3 ,  Van Tuyen Nguyen  4
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 Biologiques, 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 Biologiques, 2, Avenue du Prof L. Bernard, F-35043 Rennes Cedex, France. Electronic address: [email protected].
  • 4. Institute of Chemistry-Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Viet Nam. Electronic address: [email protected].
PMID: 25442315 DOI: 10.1016/j.bmcl.2014.09.065
Abstract

In this Letter, the synthesis and the evaluation of the cytotoxicity of new hemiasterlin analogues were reported. The indole moiety was replaced respectively by benzofurane, naphthalene and 4-bromobenzene groups. Most of these derivatives possess strong cytotoxic activity on two human tumour cell lines (KB and Hep-G2), and some analogues showed comparable cytotoxic activity to that observed for paclitaxel and ellipticine, against KB and Hep-G2 Cancer cell lines.

Keywords
Cytotoxicity; Hemiasterlin; Tripeptides; Unnatural hemiasterlin.