Design, Synthesis, Biological Evaluation, and Molecular Docking Studies of Pleuromutilin Derivatives Containing Thiazole

• DOI: 10.1021/acsinfecdis.3c00718
• Publication Date: 2024-05-04T13:16:43Z
• Authors: Ke Li; Chao Lin; Yu-Han Hu; Jun Wang; Zhen Jin; Zhen-Ling Zeng; You-Zhi Tang
• Keywords: Docking (animal); Thiazole

In this study, we designed and synthesized a series of pleuromutilin derivatives containing thiazole. The in vitro antimicrobial efficacy these compounds was examined by using four strains. Compared with tiamulin (MIC = 0.25 μg/mL), compound 14 exhibited potency inhibiting MRSA growth 0.0625 μg/mL) derivatives. Meanwhile, the time-killing kinetics further demonstrated that could efficiently inhibit growth. After exposure at 4 × MIC, postantibiotic effect (PAE) 1.29 h. Additionally, thigh-infected mice, more potent antibacterial (−1.78 ± 0.28 log10 CFU/g) reducing load compared to (−1.21 0.23 CFU/g). Moreover, MTT assay on RAW 264.7 cells (8 had no significant cytotoxicity. Docking studies indicated strong affinity toward 50S ribosomal subunit, binding free energy −9.63 kcal/mol. Taken together, it be deduced promising candidate for treating infections.