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Title: Concise synthesis and biological evaluation of 2-aroyl-5-amino benzo[b]thiophene derivatives as a novel class of potent antimitotic agents
Authors: Romagnoli, Romeo ×
Baraldi, Pier Giovanni
Lopez-Cara, Carlota
Preti, Delia
Aghazadeh Tabrizi, Mojgan
Balzarini, Jan
Bassetto, Marcella
Brancale, Andrea
Fu, Xian-Hua
Gao, Yang
Li, Jun
Zhang, Su-Zhan
Hamel, Ernest
Bortolozzi, Roberta
Basso, Giuseppe
Viola, Giampietro #
Issue Date: Nov-2013
Publisher: ACS Publications
Series Title: Journal of Medicinal Chemistry vol:56 issue:22 pages:9296-309
Article number: 10.1021/jm4013938
Abstract: The biological importance of microtubules make them an interesting target for the synthesis of antitumor agents. The 2-(3',4',5'-trimethoxybenzoyl)-5-aminobenzo[b]thiophene moiety was identified as a novel scaffold for the preparation of potent inhibitors of microtubule polymerization acting through the colchicine site of tubulin. The position of the methoxy group on the benzo[b]thiophene was important for maximal antiproliferative activity. Structure-activity relationship analysis established that the best activities were obtained with amino and methoxy groups placed at the C-5 and C-7 positions, respectively. Compounds 3c-e showed more potent inhibition of tubulin polymerization than combretastatin A-4 and strong binding to the colchicine site. These compounds also demonstrated substantial antiproliferative activity, with IC50 values ranging from 2.6 to 18 nM in a variety of cancer cell lines. Importantly, compound 3c (50 mg/kg), significantly inhibited the growth of the human osteosarcoma MNNG/HOS xenograft in nude mice.
URI: 
ISSN: 0022-2623
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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