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 C14 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 µg/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.