Title: Substituted 2-(3',4',5'-trimethoxybenzoyl)-benzo[b]thiophene derivatives as potent tubulin polymerization inhibitors
Authors: Romagnoli, Romeo ×
Baraldi, Pier Giovanni
Carrion, Maria Dora
Cruz-Lopez, Olga
Tolomeo, Manlio
Grimaudo, Stefania
Di Cristina, Antonietta
Pipitone, Maria Rosaria
Balzarini, Jan
Brancale, Andrea
Hamel, Ernest #
Issue Date: Jul-2010
Publisher: Pergamon
Series Title: Bioorganic & Medicinal Chemistry vol:18 issue:14 pages:5114-5122
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.
ISSN: 0968-0896
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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