Antimicrobial, antioxidant and cytotoxic evaluation of diazenyl chalcones along with insights to mechanism of interaction by molecular docking studies

Background In continuation of our work, new diazenyl chalcones scaffolds (C-18 to C-27) were efficiently synthesized from substituted acetophenone azo dyes (A-E) by base catalyzed Claisen-Schmidt condensation with different substituted aromatic/heteroaromatic aldehydes.Methodology The synthesized chalcones were assessed for their in vitro antimicrobial potential towards several pathogenic microbial strains by tube dilution method and further evaluated for antioxidant potential by DPPH assay. These derivatives were also assessed for the cytotoxicity towards the human lung cancer cell line (A549) and normal cell line (HEK) by MTT assay. The most active antimicrobial compounds were docked using Schrodinger v18.1 software with the various potential bacterial receptors to explore the mechanism of interaction.Results The derivative C-22 exhibited high antibacterial activity with very low MIC (1.95-3.90 µg ml-1) and MBC (3.90-7.81 µg ml-1) values. The derivatives C-23, C-24 and C-27 have demonstrated good antioxidant potential (IC50 = 7-18 µg ml-1) correlated to the ascorbic acid (IC50 = 4.45 µg ml-1). The derivative C-25 had shown comparable cytotoxicity to camptothecin against A549 cell line. The docking studies predicted the bacterial dihydrofolate reductase (PDB ID: 3SRW) and bacterial DNA gyrase (PDB ID: 4ZVI) as the possible targets for most of the active antimicrobial compounds. These derivatives affirmed their safety by presenting less cytotoxicity towards HEK cells. Further the ADME prediction by qikprop module of the Schrodinger proved that these compounds exhibited drug-like attributes.Conclusion Hence, these compounds have shown their potential as lead for future expansion of novel antimicrobial and cytotoxic drugs.