Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma

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• 作者：Ying Chen^&dagger ; ; Ling Zhang^&dagger ; ; Chao Yang^&dagger ; ; Jinsong Han ; Chongqing Wang ; Canhui Zheng ; Youjun Zhou ; Jiaguo Lv ; Yunlong Song ; ^{ylsong@smmu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Ju Zhu ; ^{zhuju@smmu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BBRINJUWZRLWKK-UHFFFAOYSA-N
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：24
• 期：5
• 页码：957-966
• 全文大小：1600 K

文摘

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is related to cellular activities. Abnormalities of this signaling pathway were discovered in various cancers, including hepatocellular carcinoma (HCC). The PI3K/mTOR dual inhibitors were proposed to have enhanced antitumor efficacies by targeting multiple points of the signaling pathway. We synthesized a series of propynyl-substituted benzenesulfonamide derivatives as PI3K/mTOR dual inhibitors. Compound 7k (NSC781406) was identified as a highly potent dual inhibitor, which exhibited potent tumor growth inhibition in the hepatocellular carcinoma BEL-7404 xenograft model. Compound 7k may be a potential therapeutic drug candidate for HCC.