Discovery and optimization of new benzofuran derivatives against p53-independent malignant cancer cells through inhibition of HIF-1 pathway

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• 作者：Ying-Rui Yang^a ; ^b ; Jin-Lian Wei^a ; ^b ; Xiao-Fei Mo^a ; ^b ; Zhen-Wei Yuan^a ; ^b ; Jia-Lin Wang^a ; ^b ; Chao Zhang^a ; ^b ; Yi-Yue Xie^a ; ^b ; Qi-Dong You^a ; ^b ; ^{youqd@163.com" class="auth_mail" title="E-mail the corresponding author} ; Hao-Peng Sun^a ; ^b ; ^c ; ^{sunhaopeng@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Benzofuran ; Antitumor ; Apoptosis ; Cycle arrest ; HIF-1 inhibition
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 June 2016
• 年：2016
• 卷：26
• 期：11
• 页码：2713-2718
• 全文大小：1877 K

文摘

p53-independent malignant cancer is still severe health problem of human beings. HIF-1 pathway is believed to play an important role in the survival and developing progress of such cancers. In the present study, with the aim to inhibit the proliferation of p53-independent malignant cells, we disclose the optimization of 6a, the starting compound which is discovered in the screening of in-house compound collection. The structure–activity relationship (SAR) is summarized. The most potent derivative 8d, inhibits the proliferation of both p53-null and p53-mutated cells through inhibition of HIF-1 pathway. Our findings here provide a new chemotype in designing potent anticancer agent especially against those p53-independent malignant tumors.