New 3-Hydroxypyridine-4-one Analogues: Their Synthesis, Antimicrobial Evaluation, Molecular Docking, and In Silico ADME Prediction

Abstract

Introduction: Drug resistance to existing antimicrobial drugs has become a serious threat to human health, which highlights the need to develop new antimicrobial agents.

Methods: In this study, a new set of 3-hydroxypyridine-4-one derivatives (6a-j) was synthesized, and the antimicrobial effects of these derivatives were evaluated against a variety of microorganisms using the microdilution method. The antimicrobial evaluation indicated that compound 6c, with an electron-donating group -OCH₃ at the meta position of the phenyl ring, was the most active compound against S. aureus and E. coli species with an MIC value of 32 μg/mL. Compound 6c was more potent than ampicillin as a reference drug.

Results: The in vitro antifungal results showed that the studied derivatives had moderate effects (MIC = 128-512 μg/mL) against C. albicans and A. niger species. The molecular modeling studies revealed the possible mechanism and suitable interactions of these derivatives with the target protein.

Conclusion: The obtained biological results offer valuable insights into the design of more effective antimicrobial agents.

Keywords: 3-hydroxypyridine-4-one; ADME prediction.; Synthesis; antibacterial; antifungal; molecular docking study.