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

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.

Keywords: Coumarin derivatives; MTT assay; anti-cancer agents; antiproliferative activity.; apoptosis; structural optimization.