Novel Oxazolidinone Derivatives Containing Quaternary Ammonium Fragments with Potent Antibacterial Potency

We reported a series of oxazolidinone derivatives containing quaternary ammonium fragments as potent antibacterial agents. Among them, compound 7a exhibited potent antibacterial activity against a range of pathogens, including MSSE (MIC = 0.12-0.25 μg/mL), MRSE (MIC = 0.25 μg/mL), MRSA (MIC = 4 μg/mL), and VRE (MIC = 2 μg/mL). Furthermore, 7a exhibited no cytotoxicity toward HepG2, Vero, or HUVEC cells and showed negligible hemolytic toxicity. Notably, 7a displayed weak inhibition of MAO-A and MAO-B with IC₅₀ values of 17.77 and 240.1 μM, respectively. In contrast, linezolid exhibited potent inhibitory effects on MAO-B (IC₅₀ = 1.618 μM). In addition, 7a showed concentration-dependent bactericidal effects against S. aureus ATCC 33591. Molecular docking studies revealed that 7a not only formed hydrogen bonding interactions with its target but also established a salt bridge interaction to stabilize its molecular conformation. Overall, 7a combined superior antibacterial potency with excellent safety, which warrants further investigation.