Discovery and optimization of a series of 2-aryl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazoles as novel anticancer agents.

Journal of Medicinal Chemistry
Romeo RomagnoliGiampietro Viola

Abstract

A new series of tubulin polymerization inhibitors based on the 2-aryl/heteroaryl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole scaffold was synthesized and evaluated for growth inhibition activity on a panel of cancer cell lines, cell cycle effects, and in vivo potency. Structure-activity relationships were elucidated with various substitutions at the 2-position of the thiazole skeleton. Hydrophobic moieties, such as phenyl and 3-thienyl, were well tolerated at this position, and variation of the phenyl substituents had remarkable effects on potency. The most active compound (3b) induced apoptosis through the mitochondrial pathway with activation of caspase-3. We also showed that it has potential antivascular activity since it reduced in vitro endothelial cell migration and disrupted capillary-like tube formation at noncytotoxic concentrations. Furthermore, compound 3b significantly reduced the growth of the HT-29 xenograft in a nude mouse model, suggesting that 3b is a promising new antimitotic agent with clinical potential.

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Citations

Sep 23, 2014·European Journal of Medicinal Chemistry·Ramandeep KaurJitender Bariwal
Jul 18, 2019·Future Medicinal Chemistry·Adileh AyatiAlireza Foroumadi
May 22, 2019·Current Topics in Medicinal Chemistry·Fateme AzimiLuciana Scotti
May 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Paola OlivaRomeo Romagnoli
Jul 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ashraf A AlyElshimaa M N Abdelhafez
Jan 6, 2021·European Journal of Medicinal Chemistry·Virginia SpanòPaola Barraja
Feb 8, 2021·European Journal of Medicinal Chemistry·Romeo RomagnoliRoberta Bortolozzi
Jan 18, 2018·European Journal of Medicinal Chemistry·Adileh AyatiAlireza Foroumadi
Sep 19, 2020·Current Topics in Medicinal Chemistry·Zhen ZhangQing-Shan Li

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