Design, Synthesis, Biological Activity and Molecular Docking Study of Coumarin Derivatives Bearing 2-Methylbiphenyl Moiety
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-L1inhibitory 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.
KeywordsCoumarin 2-Methylbiphenyl Anticancer activity PD-1/PD-L1 inhibitory activity Molecular docking
Unable to display preview. Download preview PDF.
- Chupak L. S., Zhang X. F., Compounds Useful as Immunomodulators, WO2015034820, 2015Google Scholar
- Pan S., Wu X., Jiang J., Gao W., Wan Y., Cheng D., Han D., Liu J., Englund N. P., Wang Y., Peukert S., Miller-Moslin K., Yuan J., Guo R., Matsumoto M., Vattay A., Jiang Y., Tsao J., Sun F., Pferdekamper A. C., Dodd S., Tuntland T., Maniara W., Kelleher J. F., Yao Y. M., Warmuth M., Williams J., Dorsch M., ACS Medicinal Chemistry Letters, 2010, 1(3), 130CrossRefGoogle Scholar
- Tauchi T., Arthrit. Res. Ther., 2012, 14(Suppl. 1), O43Google Scholar