Tubulin binding, protein-bound conformation in solution, and antimitotic cellular profiling of noscapine and its derivatives

  • J Med Chem. 2012 Mar 8;55(5):1920-5. doi: 10.1021/jm200848t.
Youssef L Bennani  1 ,  Wenxin Gu ,  Angeles Canales ,  Fernando J Díaz ,  Brenda K Eustace ,  Russell R Hoover ,  Jesus Jiménez-Barbero ,  Azin Nezami ,  Tiansheng Wang
Affiliations
  • 1. Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge Massachusetts 02139, USA. [email protected]
PMID: 22320354 DOI: 10.1021/jm200848t
Abstract

Noscapine and its 7-hydroxy and 7-amino derivatives were characterized for their binding to tubulin. A solution NMR structure of these compounds bound to tubulin shows that noscapine and its 7-aniline derivative do not compete for the same binding site nor does its small molecule crystal structure match its tubulin-bound conformation. These compounds were also tested for their antiproliferative effects on a panel hepatocellular carcinoma cell lines.