Synthesis, in vitro and in vivo evaluation of novel substituted N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methyl-quinazolin-4-amines as potent antitumor agents

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• 作者：Dong Cao^a ; ^&dagger ; ; Xiaoyan Wang^a ; ^&dagger ; ; Lei Lei^a ; ^&dagger ; ; Liang Ma^b ; Fang Wang^a ; Chunyu Wang^a ; Minghai Tang^a ; Wei Xiang^a ; Taijin Wang^a ; Hongyang Li^a ; Lijuan Chen^a ; ^{chenlijuan125@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：4-Anilinoquinazoline derivatives ; Anti-proliferation ; G2/M arrest
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：26
• 期：8
• 页码：1931-1935
• 全文大小：1189 K

文摘

A novel series of substituted N-(4-(2-(4-benzylpiperazin-1-yl)ethoxy)phenyl)-N-methylquinazolin-4-amines were synthesized and evaluated for their in vitro antiproliferative activity. Among them, compound rong class="boldFont">7arong> exhibited the best potency, with IC₅₀ values of 0.029–0.147 μM against four types of cancer cell lines. In addition, rong class="boldFont">7arong> was confirmed that it could arrest the cell cycle at G₂/M phase and trigger apoptosis. Indirect immunofluorescence staining revealed its anti-tubulin property. Importantly, rong class="boldFont">7arong> significantly inhibited tumor growths in HepG2 xenograft models without causing significant loss of body weight, suggesting that rong class="boldFont">7arong> is a promising new anticancer agent to be developed.