The central role of microtubules in cell division and mitosis makes them a particularly important target for anticancer agents. On our early publication, we found that a series of 2-(3',4',5'-trimethoxybenzoyl)-3-aminobenzo[b]thiophenes exhibited strong antiproliferative activity in the submicromolar range and significantly arrested cells in the G2-M phase of the cell cycle and induced apoptosis. In order to investigate the importance of the amino group at the 3-position of the benzo[b]thiophene skeleton, the corresponding 3-unsubstituted and methyl derivatives were prepared. A novel series of inhibitors of tubulin polymerization, based on the 2-(3,4,5-trimethoxybenzoyl)-benzo[b]thiophene molecular skeleton with a methoxy substituent at the C-4, C-5, C-6 or C-7 position on the benzene ring, was evaluated for antiproliferative activity against a panel of five cancer cell lines, for inhibition of tubulin polymerization and for cell cycle effects. Replacing the methyl group at the C-3 position resulted in increased activity compared with the corresponding 3-unsubstituted counterpart. The structure-activity relationship established that the best activities were obtained with the methoxy group placed at the C-4, C-6 or C-7 position. Most of these compounds exhibited good growth inhibition activity and arrest K562 cells in the G2-M phase via microtubule depolymerization.

Romagnoli, R., Baraldi, P.G., Carrion, M.D., Cruz-Lopez, O., Tolomeo, M., Grimaudo, S., et al. (2010). Substituted 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]thiophene derivatives as potent tubulin polymerization inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 18(14), 5114-5122 [10.1016/j.bmc.2010.05.068].

Substituted 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]thiophene derivatives as potent tubulin polymerization inhibitors

GRIMAUDO, Stefania;DI CRISTINA, Antonietta;PIPITONE, Rosaria Maria;
2010-01-01

Abstract

The central role of microtubules in cell division and mitosis makes them a particularly important target for anticancer agents. On our early publication, we found that a series of 2-(3',4',5'-trimethoxybenzoyl)-3-aminobenzo[b]thiophenes exhibited strong antiproliferative activity in the submicromolar range and significantly arrested cells in the G2-M phase of the cell cycle and induced apoptosis. In order to investigate the importance of the amino group at the 3-position of the benzo[b]thiophene skeleton, the corresponding 3-unsubstituted and methyl derivatives were prepared. A novel series of inhibitors of tubulin polymerization, based on the 2-(3,4,5-trimethoxybenzoyl)-benzo[b]thiophene molecular skeleton with a methoxy substituent at the C-4, C-5, C-6 or C-7 position on the benzene ring, was evaluated for antiproliferative activity against a panel of five cancer cell lines, for inhibition of tubulin polymerization and for cell cycle effects. Replacing the methyl group at the C-3 position resulted in increased activity compared with the corresponding 3-unsubstituted counterpart. The structure-activity relationship established that the best activities were obtained with the methoxy group placed at the C-4, C-6 or C-7 position. Most of these compounds exhibited good growth inhibition activity and arrest K562 cells in the G2-M phase via microtubule depolymerization.
2010
Romagnoli, R., Baraldi, P.G., Carrion, M.D., Cruz-Lopez, O., Tolomeo, M., Grimaudo, S., et al. (2010). Substituted 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]thiophene derivatives as potent tubulin polymerization inhibitors. BIOORGANIC & MEDICINAL CHEMISTRY, 18(14), 5114-5122 [10.1016/j.bmc.2010.05.068].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/73829
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