Design,synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors |
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| Authors: | Dong Cai Zhi hua Zhang Yu Chen Chao Ruan Sheng qiang Li Shi qin Chen Lian shan Chen |
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| Affiliation: | College of Public Basic Sciences, Jinzhou Medical University, Jinzhou 121001 China ; School of Chemical and Environmental Engineering, Liaoning University of Technology, Jinzhou 121001 China ; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016 China ; College of Pharmacy, Jinzhou Medical University, Jinzhou 121001 China, |
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| Abstract: | ![]()
A series of novel amide-linked 18β-glycyrrhetinic acid derivatives were developed by incorporating substituted piperazine amide fragments into the C30–COOH of 18β-glycyrrhetinic acid scaffold. The synthesized compounds were evaluated for their anticancer activity against Karpas299, A549, HepG2, MCF-7, and PC-3 cell lines by MTT assay. Besides, some compounds with electron-withdrawing groups on phenyl moieties exhibited noticeable antiproliferative activity. The most potent compound 4a was also found to be non-toxic to normal human hepatocytes LO2 cells. The compound 4a exhibited moderate inhibitory activity against wild-type ALK with an IC50 value of 203.56 nM and relatively weak potent activity to c-Met (IC50 > 1000 nM). Molecular docking studies were performed to explore the diversification in bonding patterns between the compound 4a and Crizotinib.Novel amide-linked 18β-glycyrrhetinic acid derivatives were synthesized as potential ALK inhibitors. |
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