Synthesis of pyrazolone derivatives of coumarin as anticancer agents

Abstract

Pursuing on our efforts towards searching for efficient anticancer agents herein we have designed and synthesized pyrazolone derivatives of 7-amino 4-methyl coumarin and 6-amino coumarin. Anticancer activity of all the compounds were performed against lungs cancer cell line (A549) and breast cancer cell line (MCF-7) using MTT assay. Out of all the compounds, compounds 17 c and 19 b exhibited remarkable activity with IC50 value of 1.22 μM and 1.66 μM against lungs cancer cell line (A549) breast cancer cell line (MCF-7) respectively. Consequently, both compounds 17 c and compound 19 b were selected to study their cytotoxicity mechanism using different assays which includes EtBr/AO assay in respective cell, quantification of ROS using DCFH-DA dye. To explore the behavioral and selective properties of the synthesized molecules, experimental analysis was complemented with computational methods. The electronic and structural parameters for both compound 17 c and 19 b were calculated using density functional theory (DFT) calculations and correlated with the observed biological activity. Molecular docking was conducted to explore the interaction of compounds 17 c and 19 b with pivotal apoptotic genes, namely p53 and caspase 3. Compound 17 c exhibited docking scores of −8.6 and −8.4 kcal/mol for p53 and caspase 3, while compound 19 b showed scores of −9.3 kcal/mol for both genes, significantly surpassing fluorouracil. Hence, compound 17 c and 19 b can be pursued for further studies, including molecular and In Vivo investigations.