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Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors.

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.

SUBMITTER: Cai D

PROVIDER: S-EPMC9050490 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors.

Cai Dong D Zhang Zhi Hua ZH Chen Yu Y Ruan Chao C Li Sheng Qiang SQ Chen Shi Qin SQ Chen Lian Shan LS

RSC advances 20200323 20

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 f ...[more]

PMID: 35496614

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