Synthesis and Biological Activities of Oxazolidinone Pleuromutilin Derivatives as a Potent Anti-MRSA Agent

• DOI: 10.1021/acsinfecdis.3c00162
• Publication Date: 2023-08-23T11:04:58Z
• Authors: Jing Xia; Yun Li; Cailu He; Can Yong; Li Wang; Huan Fu; Xiao-Long He; Zhou-Yu Wang; Dong-Fang Liu; Yuan-Yuan Zhang
• Keywords: IC50

A series of pleuromutilin derivatives containing an oxazolidinone skeleton were synthesized and evaluated in vitro vivo as antibacterial agents. Most the exhibited potent activities against three strains Staphylococcus aureus (including MRSA ATCC 33591, 43300, MSSA 29213) two epidermidis MRSE 51625 MSSE 12228). Compound 28 was most active agent (MIC = 0.008-0.125 μg·mL-1) a significant bactericidal effect, low cytotoxicity, weak inhibition (IC50 20.66 μmol·L-1) for CYP3A4, well less possibility to cause bacterial resistance. Furthermore, indicated that compound effective reducing load murine thigh infection model. Moreover, it clearly facilitated healing skin inhibited secretion TNF-α, IL-6, MCP-1 inflammatory factors serum. These results suggest is promising therapeutic candidate drug-resistant infections.