Synthesis and Antibacterial Activity Against MRSA of Pleuromutilin Derivatives Possessing a Mercaptoethylamine Linker

作者：Zhang, Zhao-Sheng; Huang, Yun-Zhen; Luo, Jian; Wang, Bing-Feng; Jin, Zhen; Liu, Ya-Hong; Tang, You-Zhi^*

来源：Medicinal Chemistry, 2018, 14(6): 585-594.

DOI：10.2174/1573406414666180416131737

• Antibacterial activity
• antibiotics
• Antibacterial Activity
• pleuromutilin
• MRSA
• molecular docking

Background: Methicillin resistant Staphylococcus aureus (MRSA) usually invalidate powerful antibiotics in the clinic. Pleuromutilin derivatives have been reported to possess antibacterial activity against MRSA. @@@ Objective: The antibacterial activities against MRSA of a series of thirteen synthetic pleuromutilin derivatives were investigated through in vitro models. @@@ Methods: A series of novel thioehter pleuromutilin derivatives incorporating various aromatic substituents into the C 14 side chain have been reported. The in vitro antibacterial activities of these derivatives against MRSA and Escherichia coli were tested by the broth dilution method. @@@ Results: Twelve pleuromutilin derivatives were designed, synthesized and evaluated for in vitro antibacterial activities against four Staphylococcus aureus strains. From structure-activity relationship studies, compound 11c was identified as promising compounds with the most potent in vitro antibacterial activity among the series (MIC = 0.0625-0.125 mu g/ml) against Staphylococcus aureus strains. The binding of compound 11c to the 50s ribosome was investigated by molecular modeling. @@@ Conclusion: It was found that there is a reasonable correlation between the binding free energy and the antibacterial activity.

• 单位
  华南热带农业大学; 华南农业大学