Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors

  • Bioorg Med Chem Lett. 2005 Dec 1;15(23):5154-9. doi: 10.1016/j.bmcl.2005.08.056.
Xiaohu Ouyang  1 ,  Xiaoling Chen ,  Evgueni L Piatnitski ,  Alexander S Kiselyov ,  Hai-Ying He ,  Yunyu Mao ,  Vatee Pattaropong ,  Yang Yu ,  Ki H Kim ,  John Kincaid ,  Leon Smith 2nd ,  Wai C Wong ,  Sui Ping Lee ,  Daniel L Milligan ,  Asra Malikzay ,  James Fleming ,  Jason Gerlak ,  Dhanvanthri Deevi ,  Jacqueline F Doody ,  Hui-Hsien Chiang ,  Sheetal N Patel ,  Ying Wang ,  Robin L Rolser ,  Paul Kussie ,  Marc Labelle ,  M Carolina Tuma
Affiliations
  • 1. Department of Chemistry, ImClone Systems, 710 Parkside Avenue, Suite 2, Brooklyn, NY 11226, USA. [email protected]
PMID: 16198562 DOI: 10.1016/j.bmcl.2005.08.056
Abstract

A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 Cancer cells with EC(50) values in the single digit nanomolar range. Binding experiments demonstrated that representative active compounds of this class compete with colchicine for its binding site on tubulin. The syntheses and structure-activity relationship studies for the triazole derivatives are described herein.