Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization
Romagnoli, Romeo × Baraldi, Pier Giovanni Carrion, Maria Dora Lopez Cara, Carlota Preti, Delia Fruttarolo, Francesca Pavani, Maria Giovanna Tabrizi, Mojgan Aghazadeh Tolomeo, Manlio Grimaudo, Stefania Di Cristina, Antonella Balzarini, Jan Hadfield, John A Brancale, Andrea Hamel, Ernest #
Journal of Medicinal Chemistry vol:50 issue:9 pages:2273-2277
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.