Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization

  • J Med Chem. 2007 May 3;50(9):2273-7. doi: 10.1021/jm070050f.
Romeo Romagnoli  1 ,  Pier Giovanni Baraldi ,  Maria Dora Carrion ,  Carlota Lopez Cara ,  Delia Preti ,  Francesca Fruttarolo ,  Maria Giovanna Pavani ,  Mojgan Aghazadeh Tabrizi ,  Manlio Tolomeo ,  Stefania Grimaudo ,  Antonella Di Cristina ,  Jan Balzarini ,  John A Hadfield ,  Andrea Brancale ,  Ernest Hamel
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy.
PMID: 17419607 DOI: 10.1021/jm070050f
Abstract

Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits Cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.