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

doi:10.1007/s40242-019-8310-7

高等学校化学研究 ›› 2019, Vol. 35 ›› Issue (3): 410-417.doi: 10.1007/s40242-019-8310-7

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

MA Junjie¹, HUANG Kun¹, NI Xin¹, CHEN Roufen¹, XU Boxuan², WANG Cuifang³

1. School of Medicine, Huaqiao University, Quanzhou 362000, P. R. China;
2. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
3. College of Oceanology and Food Science, Quanzhou Normal University, Quanzhou 362000, P. R. China

收稿日期:2018-09-25 修回日期:2019-02-28 出版日期:2019-06-01 发布日期:2019-03-27
通讯作者: MA Junjie, WANG Cuifang E-mail:majunjie3612@hqu.edu.cn;wlycf@163.com
基金资助:
Supported by the National Natural Science Foundation of China(No.81602970), the Promotion Program for Young and Mid-dle-aged Teacher in Science and Technology Research of Huaqiao University, China(No.ZQN-PY519), the Science and Techno- logy Project of Quanzhou City, China(No.2018C074R) and the Subsidized Project for Postgraduates' Innovative Fund in Scientific Research of Huaqiao University, China.

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

MA Junjie¹, HUANG Kun¹, NI Xin¹, CHEN Roufen¹, XU Boxuan², WANG Cuifang³

1. School of Medicine, Huaqiao University, Quanzhou 362000, P. R. China;
2. Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China;
3. College of Oceanology and Food Science, Quanzhou Normal University, Quanzhou 362000, P. R. China

Received:2018-09-25 Revised:2019-02-28 Online:2019-06-01 Published:2019-03-27
Contact: MA Junjie, WANG Cuifang E-mail:majunjie3612@hqu.edu.cn;wlycf@163.com
Supported by:
Supported by the National Natural Science Foundation of China(No.81602970), the Promotion Program for Young and Mid-dle-aged Teacher in Science and Technology Research of Huaqiao University, China(No.ZQN-PY519), the Science and Techno- logy Project of Quanzhou City, China(No.2018C074R) and the Subsidized Project for Postgraduates' Innovative Fund in Scientific Research of Huaqiao University, China.

摘要/Abstract

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-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.

关键词: Coumarin, 2-Methylbiphenyl, Anticancer activity, PD-1/PD-L1 inhibitory activity, Molecular docking

Abstract: 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.

Key words: Coumarin, 2-Methylbiphenyl, Anticancer activity, PD-1/PD-L1 inhibitory activity, Molecular docking

MA Junjie, HUANG Kun, NI Xin, CHEN Roufen, XU Boxuan, WANG Cuifang. Design, Synthesis, Biological Activity and Molecular Docking Study of Coumarin Derivatives Bearing 2-Methyl b iphenyl Moiety[J]. 高等学校化学研究, 2019, 35(3): 410-417.

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

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

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