Design, Synthesis and Biological Evaluation of 4, 6-Coumarin Derivatives as Anti- Cancer and Apoptosis-Inducing Agents

Author(s):

Guoyi Yan, Jiang Luo , Xuan Han, Wenjuan Zhang , Chunlan Pu, Meng Zhou, Xinxin Zhong, Xueyan Hou, Man Zhou Hou and Rui Li *   Pages 2351 - 2367 ( 17 )

Abstract:

<P>Background: Coumarin structures were widely employed in anti-cancer drug design. Herein we focused on the modifications of C4 and C6 positions on coumarin scaffold to get novel anti-cancer agents. </P><P> Objective: The objective of the current work was the synthesis and biological evaluation of a series of 4, 6-coumarin derivatives to get novel anticancer agents. </P><P> Methods: Thirty-seven coumarin derivatives were designed and synthesized, the antiproliferative activity of the compounds was evaluated against human cancer cell lines and non-cancerous cells by MTT assay. The bioactivities and underlying mechanisms of active molecules were studied and the ADMET characters were predicted. </P><P> Results: Among the compounds, 4-p-hydroxy phenol-6-pinacol borane coumarin (25) exhibited a promising anti- cancer activity to cancer cell lines in a dose-dependent manner and the toxicity to normal cells was low. The mechanism of action was observed by inducing G₂/M phase arrest and apoptosis which was further confirmed via western blot. In silico ADMET prediction revealed that compound 25 is a drug-like small molecule with a favorable safety profile. </P><P> Conclusion: The findings in this work may give vital information for further development of 6-pinacol borane coumarin derivatives as novel anti-cancer agents.</P>

Keywords:

Coumarin derivatives, structural optimization, anti-cancer agents, MTT assay, apoptosis, antiproliferative activity.

Affiliation:

State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education & State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550004, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, College of Pharmacy, Xinxiang Medical University, Xinxiang, 453003, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041

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