Isocombretastatins a versus combretastatins a: the forgotten isoCA-4 isomer as a highly promising cytotoxic and antitubulin agent

  • J Med Chem. 2009 Jul 23;52(14):4538-42. doi: 10.1021/jm900321u.
Samir Messaoudi  1 ,  Bret Tréguier ,  Abdallah Hamze ,  Olivier Provot ,  Jean-François Peyrat ,  Jordi Rodrigo De Losada ,  Jian-Miao Liu ,  Jérôme Bignon ,  Joanna Wdzieczak-Bakala ,  Sylviane Thoret ,  Joëlle Dubois ,  Jean-Daniel Brion ,  Mouâd Alami
Affiliations
  • 1. Laboratoire de Chimie Therapeutique, Faculte de Pharmacie, Univ Paris-Sud, CNRS, BioCIS-UMR 8076, Clement, Chatenay-Malabry F-92296, France.
PMID: 19530698 DOI: 10.1021/jm900321u
Abstract

Herein is reported a convergent synthesis of isocombretastatins A, a novel class of potent antitubulin agents. These compounds having a 1,1-diarylethylene scaffold constitute the simplest isomers of natural Z-combretastatins A that are easy to synthesize without need to control the Z-olefin geometry. The discovery of isoCA-4 with biological activities comparable to that of CA-4 represents a major progress in this field.