Computational identification of carotol as a potent inhibitor of PDC-3 and NDM-1 β-lactamases in Pseudomonas aeruginosa

Nosocomial infections caused by Pseudomonas aeruginosa ( P. aeruginosa ) display a significant threat with high levels of multi-drug resistance against current antibiotic treatments. Beta-lactamases (BLs) are major contributors to resistance acquisition against beta-lactams. Pseudomonas -derived cephalosporinase (PDC-3) and New Delhi Metallo beta-lactamases (NDM-1) are frequently occurring BLs in Carbapenem Resistant P. aeruginosa (CRPA) population, in India. The study evaluates phytocompounds for their beta-lactamase inhibitory potential against PDC-3 and NDM-1 of P. aeruginosa , employing an in-silico approach. Phytocompounds were screened for their drug likeness based on pharmacokinetic and toxicity parameters, followed by molecular docking, molecular dynamics simulations, and density functional theory analyses. Carotol emerged as the most promising candidate, possessing favourable docking scores of −5.92 kcal/mol and − 5.94 kcal/mol with PDC-3 NDM-1, respectively. Molecular dynamics simulations further confirmed stable and consistent interactions of carotol with both enzymes. Although the in vitro validations would strengthen the proposal of carotol as a potent beta-lactamase inhibitor. • Carbapenem-resistant Pseudomonas aeruginosa possesses significant threat among nosocomial pathogens with increasing multi-drug resistance, high morbidity and mortality rates. • The study evaluates beta-lactamase inhibitor activity of phytocompounds against frequently occurring beta-lactamases, PDC-3 and NDM-1 in Pseudomonas aeruginosa via employing in silico approach. • Carotol depicts good binding affinities and intermolecular interactions with both BLs, PDC-3 and NDM-1, along with suitable Pharmacokinetics and toxicity profiles. • Carotol phytocompound can serve as potential beta-lactamase inhibitor against P. aeruginosa infections, post in vitro evaluation.