Design, Synthesis, Biological Activity and Molecular Docking Study of Coumarin Derivatives Bearing 2-Methylbiphenyl Moiety

• 来源期刊: 高等学校化学研究（英文版）
• 年，卷（期）: 2019,（3）
• 页码范围: 410-417
• 页数: 8页
• 语种: 英文
• DOI: 10.1007/s40242-019-8310-7

摘要

A hybrid pharmacophore approach was used to design and synthesize a series of coumarin derivatives bearing 2-methylbiphenyl moiety,which were evaluated for their in vitro anticancer activities against four cancer cell lines(MCF-7,A549,H460 and HT29) and PD-1/PD-L1 inhibitory activities.Moreover,several compounds with excellent anticancer activities were selected to evaluate the cytotoxicities against one normal cell line(HEK-293).The most promising compound 11o showed the best anticancer activities against the four tested cancer cell lines with the IC50 values of 6.45,8.65,6,57 and 8.13 μmol/L,respectively,and displayed weak cytotoxicity on the normal cell(HEK-293).Furthermore,screening of PD-1/PD-Llinhibitory activity revealed that compound 11o could effectively inhibit the binding of PD-1/PD-L1,and the binding interactions of compound 11o with PD-L1 protein were explored by molecular docking.All above evidences showed that compound 11o might be worthy of further study as a valuable leading compound for the treatment of cancer.