Aims: In this study, novel synthesized 1,6-disubstituted-1-azacoumarin-3-carboxylic acid derivatives were designed, synthesized and evaluated as potential anticancer agents. Materials & methods: The cytotoxicity of novel 1-azacoumarin-3-carboxylic acid derivatives was tested using an MTT assay. High potency was shown by DNA flow cytometry on MCF-7 cells for compound 3b. In addition, topoisomerase IIβ, caspase 3/7, Bax and Bcl-2 enzymes were used to study apoptotic activity. In the same studies, molecular docking analysis assessed activity. Results & conclusion: Cytotoxicity screening identified multiple bioactive compounds, especially compound 3b. Analysis of DNA flow cytometry revealed that compound 3b exhibited cell cycle arrest. Compound 3b had an increase in the expression of Bax/Bcl-2 ratio and caspase 3/7, and a decrease in topoisomerase IIβ enzyme inhibition.
Keywords: Bax/Bcl2; MCF-7; anticancer; azacoumarin; caspase 3/7; cytotoxicity; docking.