Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymerization

  • Bioorg Med Chem. 2008 Sep 15;16(18):8419-26. doi: 10.1016/j.bmc.2008.08.029.
Romeo Romagnoli  1 ,  Pier Giovanni Baraldi ,  Taradas Sarkar ,  Maria Dora Carrion ,  Olga Cruz-Lopez ,  Carlota Lopez Cara ,  Manlio Tolomeo ,  Stefania Grimaudo ,  Antonietta Di Cristina ,  Maria Rosaria Pipitone ,  Jan Balzarini ,  Roberto Gambari ,  Lampronti Ilaria ,  Roberto Saletti ,  Andrea Brancale ,  Ernest Hamel
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy. [email protected]
PMID: 18755591 DOI: 10.1016/j.bmc.2008.08.029
Abstract

Molecules that target microtubules have an important role in the treatment of Cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits Cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.