Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment

  • Bioorg Med Chem Lett. 2004 Nov 1;14(21):5317-22. doi: 10.1016/j.bmcl.2004.08.024.
Ayako Yamashita  1 ,  Emily B Norton ,  Joshua A Kaplan ,  Chuan Niu ,  Frank Loganzo ,  Richard Hernandez ,  Carl F Beyer ,  Tami Annable ,  Sylvia Musto ,  Carolyn Discafani ,  Arie Zask ,  Semiramis Ayral-Kaloustian
Affiliations
  • 1. Chemical and Screening Sciences and Oncology Research, Wyeth Research, Pearl River, NY 10965, USA. [email protected]
PMID: 15454219 DOI: 10.1016/j.bmcl.2004.08.024
Abstract

Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization. The structure-activity relationships related to stereo- and regio-chemical effects of substituents on the aromatic ring in the A segment were studied. Analogs, which carry a meta-substituted phenyl ring in the A segment show comparable activity for inhibition of tubulin polymerization to 2, as well as in the cell proliferation assay using KB cells containing P-glycoprotein, compared to those of 1 and 2.