当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole: a unique, highly active antimicrotubule agent.

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

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.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Romagnoli R,Baraldi PG,Lopez Cara C,Kimatrai Salvador M,Bortolozzi R,Basso G,Viola G,Balzarini J,Brancale A,Fu XH,Li J,Zhang SZ,Hamel E

doi

10.1016/j.ejmech.2011.10.013

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

6015-24

issue

12

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(11)00730-6

journal_volume

46

pub_type

杂志文章

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