Jan Balzarini, Francesca Fruttarolo, Delia Preti, John A. Hadfield, Mojgan Aghazadeh Tabrizi, and Andrea Brancale, Ernest Hamel, Maria Giovanna Pavani, Pier Giovanni Baraldi, Carlota Lopez Cara, Stefania Grimaudo, Manlio Tolomeo, Maria Dora Carrion, Romeo Romagnoli, Antonella Di Cristina, ROMAGNOLI R, BARALDI PG, CARRION MD, CARA CL, PRETI D, FRUTTAROLO F, PAVANI MG, TABRIZI MA, TOLOMEO M, GRIMAUDO S, DI CRISTINA A, BALZARINI J, HADFIELD JA, BRANCALE A, and HAMEL E
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.