Convergent Synthesis and Biological Evaluation of 2-Amino-4-(3′,4′,5′-trimethoxyphenyl)-5-aryl Thiazoles as Microtubule Targeting Agents

Romagnoli, Romeo, Baraldi, Pier Giovanni, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Ricci, Antonio, Hamel, Ernest, Bortolozzi, Roberta, Basso, Giuseppe and Viola, Giampietro 2011. Convergent Synthesis and Biological Evaluation of 2-Amino-4-(3′,4′,5′-trimethoxyphenyl)-5-aryl Thiazoles as Microtubule Targeting Agents. Journal of Medicinal Chemistry 54 (14) , pp. 5144-5153. 10.1021/jm200392p

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Abstract

Combretastatin A-4, a potent tubulin polymerization inhibitor, caused us to synthesize a novel series of 2-amino-4-(3′,4′,5′-trimethoxyphenyl)-5-aryl thiazoles with the goal of evaluating the effects of substituents on the phenyl at the 5-position of the thiazole skeleton on biological activities. An ethoxy group at the para-position produced the most active compound in the series, with IC50 values of 0.03–0.9 nM against five of seven cancer cell lines. The most active compounds retained full activity in multidrug resistant cancer cells and acted through the colchicine site of tubulin. Treated cells were arrested in the G2/M phase of the cell cycle, with cell death proceeding through an apoptotic pathway that was only partially caspase-dependent. Preliminary results suggest that, in addition to cell death by apoptosis, cells were also killed via mitotic catastrophe as an alternative cell death mechanism.

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:	05 Jan 2024 05:58
URI:	https://orca.cardiff.ac.uk/id/eprint/7449

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