Design, synthesis and antibacterial activities of pleuromutilin derivatives

Abstract

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 μg/ml. 10a and 10 b showed similar activity to positive control drugs (tiamulin, erythromycin) against S. aureus with the MIC value of 0.125 μg/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.

Graphical Abstract

Keywords:

• Pleuromutilin derivatives
• antibacterial activity
• design
• synthesis
• Gram-positive bacteria

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was funded by the Research Project of Hebei Administration of Chinese Medicine [No. 2019080], Doctor Foundation of Hebei University of Chinese Medicine [No. BSZ2018006] and Basic Research Program of Outstanding Young Teachers of Hebei University of Chinese Medicine [No. YQ2018004].