Design, synthesis and antibacterial activities of pleuromutilin derivatives

We described the design, synthesis and antimicrobial activities of novel pleuromutilin derivatives with substituted piperazine substrate. Minimum inhibitory concentration (MIC) was used to evaluate the activity of the derivatives against six bacteria in vitro, and compound 8 was potent against Staphylococcus aureus and Staphylococcus epidermidis with the MIC value of 0.0625 mu g/ml. 10a and 10 b showed similar activity to positive control drugs (tiamulin, erythromycin) against S. aureus with the MIC value of 0.125 mu g/ml. The binding mode of compound 8 and tiamulin to the ribosome pocket showed the correlation between binding parameters and the antibacterial activity, and more bonds and stronger combination could effectively enhance the activity of compounds.

Automated summary

Novel pleuromutilin derivatives were synthesized and compound 8 showed potent antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis. Compound 8 and tiamulin binding to the ribosome pocket demonstrated that more bonds and stronger combination could enhance the antimicrobial activity of the compounds.