Novel Oxazolidinone Derivatives Containing Quaternary Ammonium Fragments with Potent Antibacterial Potency

作者：Chenghong Zheng, Minghua Wang, Ying Wang, Ying Wang, Xiukun Wang, Ying Han, Xuefu You, Xinxin Hu, Mei Zhu, Guoning Zhang, Liyan Yu, Yucheng Wang, Yucheng Wang, Juxian Wang · 发表于：ACS Medicinal Chemistry Letters · 年份：2025 · DOI：10.1021/acsmedchemlett.5c00317 · 被引用次数：2 · 研究领域：Synthesis and biological activity、Synthesis and Biological Evaluation、Phenothiazines and Benzothiazines Synthesis and Activities

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 IC 50 values of 17.77 and 240.1 μM, respectively. In contrast, linezolid exhibited potent inhibitory effects on MAO-B (IC 50 = 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.