Synthesis, Antimitotic and Antivascular Activity of 1-(3鈥?4鈥?5鈥?Trimethoxybenzoyl)-3-arylamino-5-amino-1,2,4-triazoles
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- 作者：Romeo Romagnoli ; Pier Giovanni Baraldi ; Maria Kimatrai Salvador ; Filippo Prencipe ; Valerio Bertolasi ; Michela Cancellieri ; Andrea Brancale ; Ernest Hamel ; Ignazio Castagliuolo ; Francesca Consolaro ; Elena Porc霉 ; Giuseppe Basso ; Giampietro Viola
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：August 14, 2014
- 年：2014
- 卷：57
- 期：15
- 页码：6795-6808
- 全文大小：605K
- ISSN：1520-4804
文摘
A new class of compounds that incorporated the structural motif of the 1-(3鈥?4鈥?5鈥?trimethoxtbenzoyl)-3-arylamino-5-amino-1,2,4-triazole molecular skeleton was synthesized and evaluated for their antiproliferative activity in vitro, interactions with tubulin, and cell cycle effects. The most active agent, 3c, was evaluated for antitumor activity in vivo. Structure鈥揳ctivity relationships were elucidated with various substituents on the phenyl ring of the anilino moiety at the C-3 position of the 1,2,4-triazole ring. The best results for inhibition of cancer cell growth were obtained with the p-Me, m,p-diMe, and p-Et phenyl derivatives 3c, 3e, and 3f, respectively, and overall, these compounds were more or less as active as CA-4. Their vascular disrupting activity was evaluated in HUVEC cells, with compound 3c showing activity comparable with that of CA-4. Compound 3c almost eliminated the growth of syngeneic hepatocellular carcinoma in Balb/c mice, suggesting that 3c could be a new antimitotic agent with clinical potential.