One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole: A unique, highly active antimicrotubule agent

Romagnoli, Romeo, Baraldi, Pier Giovanni, Lopez Cara, Carlota, Kimatrai Salvador, Maria, Bortolozzi, Roberta, Basso, Giuseppe, Viola, Giampietro, Balzarini, Jan, Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419, Fu, Xian-Hua, Li, Jun, Zhang, Su-Zhan and Hamel, Ernest 2011. One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole: A unique, highly active antimicrotubule agent. European Journal of Medicinal Chemistry 46 (12) , pp. 6015-6024. 10.1016/j.ejmech.2011.10.013

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Abstract

A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring plays an essential role in compound activity. The most active agent (3f) inhibited at submicromolar concentrations the growth of tumor cell lines. It also inhibited tubulin polymerization with an activity quantitatively similar to that of CA-4, and treatment of HeLa cells resulted in their arrest at the G2-M phase of the cell cycle. Furthermore, 3f was effective against multidrug resistant cancer cells and inhibited the growth of the HT-29 xenograft in a nude mouse model. This indicated that 3f is a promising new antimitotic agent with encouraging preclinical potential.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	Microtubules; Structure-activity relationship; Thiazole; In vivo and in vitro activity; Tubulin
Publisher:	Elsevier
ISSN:	0223-5234
Last Modified:	05 Jan 2024 05:51
URI:	https://orca.cardiff.ac.uk/id/eprint/15638

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