Synthesis and Biological Evaluation of 2-(Alkoxycarbonyl)-3-Anilinobenzo[b]thiophenes and Thieno[2,3-b]pyridines as New Potent Anticancer Agents

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• 作者：Romeo Romagnoli ; Pier Giovanni Baraldi ; Maria Kimatrai Salvador ; Delia Preti ; Mojgan Aghazadeh Tabrizi ; Marcella Bassetto ; Andrea Brancale ; Ernest Hamel ; Ignazio Castagliuolo ; Roberta Bortolozzi ; Giuseppe Basso ; Giampietro Viola
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：March 28, 2013
• 年：2013
• 卷：56
• 期：6
• 页码：2606-2618
• 全文大小：600K
• 年卷期：v.56,no.6(March 28, 2013)
• ISSN：1520-4804

文摘

Two new series of inhibitors of tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3鈥?4鈥?5鈥?trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized and evaluated for antiproliferative activity on a panel of cancer cell lines, inhibition of tubulin polymerization, cell cycle effects, and in vivo potency. Antiproliferative activity was strongly dependent on the position of the methyl group on the benzene portion of the benzo[b]thiophene nucleus, with the greatest activity observed when the methyl was located at the C-6 position. Also, in the smaller thieno[2,3-b]pyridine series, the introduction of the methyl group at the C-6 position resulted in improvement of antiproliferative activity to the nanomolar level. The most active compounds (4i and 4n) did not induce cell death in normal human lymphocytes, suggesting that the compounds may be selective against cancer cells. Compound 4i significantly inhibited in vivo the growth of a syngeneic hepatocellular carcinoma in Balb/c mice.