Facile one‐pot synthesis of <i>N‐</i>pyridinylaminonaphthol derivatives and their antibacterial evaluation against multidrug‐resistant <i>Staphylococcus aureus</i>

The escalating severity of the menace posed by bacterial resistance has rendered the existing antibiotics less effective, thus necessitating the discovery of new antibacterial agents. The current study reports the exploration of substituted N-pyridinylaminonaphthols produced by a straightforward, one-pot multicomponent reaction process as antibacterial agents. The synthesized derivatives were assessed in vitro for their antibacterial properties against a panel of bacterial pathogens. The analogs 4b, 4g, 4h, 4i, 4j, 4l, 4r, and 4t exhibited potent inhibitory activity with minimum inhibitory concentration (MIC) values of 1-2 µg/mL. Notably, 4b, 4l, and 4t displayed an excellent selectivity index. Additionally, they were active against the multidrug-resistant bacterial strains, with 4l exhibiting the best activity against methicillin-resistant Staphylococcus aureus and vancomycin resistant staphylococcus aureus with a MIC of 1 µg/mL. 4l showed synergism with gentamycin and showed bactericidal property in a concentration-dependent manner. Furthermore, the molecule 4l inhibited the DNA gyrase supercoiling activity. Absorption, distribution, metabolism, excretion/toxicity parameters and pharmacokinetic properties were assessed via in silico techniques, which elucidate the potential mode of action. These findings demonstrate the potential of the N-pyridinylaminonaphthol derivatives as antibacterial agents against multidrug-resistant S. aureus.