Antioxidant and Antimicrobial Activities of 3‐Cyano‐2‐pyridones: In Vitro and In Silico Study

ABSTRACT The increasing prevalence of bacterial infections, antibiotic resistance, and oxidative stress necessitates the development of novel antimicrobial and antioxidant agents. In the present study, thirty‐seven 3‐cyano‐2‐pyridone derivatives (7a–7ak) were evaluated for their antimicrobial and DPPH radical scavenging activities. Compounds 7a , 7aj , and 7ak exhibited strong inhibitory action against gram‐negative bacteria Pseudomonas aeruginosa , with zone of inhibition 16.00, 15.90 and 15.40 mm, respectively, comparable to streptomycin with 16.00 mm zone of inhibition. Compound 7ag and 7aa were most active against gram positive bacteria Staphylococcus aureus with zone of inhibition 10.20 and 10.00 mm, respectively. In silico study using the most active molecules 7a , 7aj , and 7ag which binds to the pocket of target tyrosyl‐ t RNA synthetase from S . aureus and LasR‐OC12 HSL complex from P. aeruginosa , further confirmed the in vitro results. The binding free energy of the compounds 7a, 7aj and 7ag with Tyrosyl‐tRNA synthetase (1JIJ complex) were found to be −5.165, −5.762, −5.081 kcal/mol respectively, while with LasR‐OC12 HSL(3ix3) complex −7.43, −6.646 and −8.081 kcal/mol, respectively. The electronic properties of selected active compounds were investigated using density functional theory (DFT) calculations. Also, compounds 7o , 7p , 7q , 7t , and 7v showed moderate antioxidant but were less active than standard BHT.