Title:Design, Synthesis and Biological Evaluation of 4, 6-Coumarin Derivatives as Anti- Cancer and Apoptosis-Inducing Agents
Volume: 21
Issue: 17
Author(s): Guoyi Yan, Jiang Luo , Xuan Han, Wenjuan Zhang , Chunlan Pu, Meng Zhou, Xinxin Zhong, Xueyan Hou, Man Zhou Hou and Rui Li *
Affiliation:
- State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041,China
Keywords:
Coumarin derivatives, structural optimization, anti-cancer agents, MTT assay, apoptosis, antiproliferative activity.
Abstract:
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.
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.
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.
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.
Conclusion: The findings in this work may give vital information for further development of 6-pinacol borane
coumarin derivatives as novel anti-cancer agents.
