Discovery of a potent enoyl-acyl carrier protein reductase (FabI) inhibitor suitable for antistaphylococcal agent

Abstract

We report the discovery, synthesis, and biological activities of phenoxy-4-pyrone and phenoxy-4-pyridone derivatives as novel inhibitors of enoyl-acyl carrier protein reductase (FabI). Pyridone derivatives showed better activities than pyrone derivatives against FabI and Staphylococcus aureus strains, including methicillin-resistant Staphylococcus aureus (MRSA). Among the pyridone derivatives, compound 16l especially exhibited promising activities against the MRSA strain and good pharmacokinetic profiles.

Keywords: Antibiotic; Enoyl-acyl carrier protein reductase (FabI); MRSA; Pyridone.