Concise synthesis and biological evaluation of 2-aroyl-5-amino benzo[b]thiophene derivatives as a novel class of potent antimitotic agents

Romagnoli, Romeo, Baraldi, Pier Giovanni, Lopez-Cara, Carlota, Preti, Delia, Aghazadeh Tabrizi, Mojgan, Balzarini, Jan, Bassetto, Marcella ORCID: https://orcid.org/0000-0002-2491-5868, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Fu, Xian-Hua, Gao, Yang, Li, Jun, Zhang, Su-Zhan, Hamel, Ernest, Bortolozzi, Roberta, Basso, Giuseppe and Viola, Giampietro 2013. Concise synthesis and biological evaluation of 2-aroyl-5-amino benzo[b]thiophene derivatives as a novel class of potent antimitotic agents. Journal of Medicinal Chemistry 56 (22) , pp. 9296-9309. 10.1021/jm4013938

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Publisher:	American Chemical Society
ISSN:	0022-2623
Last Modified:	06 Jan 2024 05:13
URI:	https://orca.cardiff.ac.uk/id/eprint/56819

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