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

• Published in: Archiv der Pharmazie (Weinheim) 2024-11, Vol.357 (11), p.e2400358-n/a
• Main Authors: Bakchi, Bulti, Maddipatla, Sarvan, Gupta, Khushi, Singampalli, Anuradha, Saxena, Deepanshi, Maitra, Rahul, Agnivesh, Puja K., Kalia, Nitin P., Nanduri, Srinivas, Chopra, Siddharth, Yaddanapudi, Venkata M.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antimicrobial resistance; Betti reaction; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial - drug effects; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; Molecular Structure; multicomponent; Naphthols - chemical synthesis; Naphthols - chemistry; Naphthols - pharmacology; N‐pyridinylaminonaphthols; Staphylococcus aureus; Structure-Activity Relationship
• ISSN: 0365-6233; 1521-4184; 1521-4184
• DOI: 10.1002/ardp.202400358

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. N‐Pyridinylaminonaphthols synthesized in a one‐pot manner are reported as antibacterial agents with selective activity against Staphylococcus aureus strains. Compound 4l showed synergism with gentamycin and bactericidal properties in a concentration‐dependent manner and inhibited the DNA gyrase supercoiling activity. The potential mode of action was predicted through in silico techniques.