Design, synthesis and antibacterial activity evaluation of pleuromutilin derivatives according to twin drug theory

Abstract

A series of novel pleuromutilin derivatives were designed and synthesized based on the twin drugs theory. Piperazinyl and thioether were used as the linkage to connect the pleuromutilin nuclear and sulfonamide to improve the biological activity and water solubility of derivatives. The in vitro antibacterial activities against drug-sensitive and drug-resistance bacteria were evaluated by agar dilution method. Most of the 25 compounds displayed excellent antibacterial activities against drug-sensitive bacteria, particularly, five compounds (9, 10, 11, 14a and 14b) exerted the excellent antibacterial activities against drug-resistance bacteria.

Graphical abstract

Keywords:

• Pleuromutilin derivatives
• antibacterial activity
• design
• synthesis
• twin drugs theory

Disclosure statement

The authors declare that they have no conflict of interest.

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), Basic Research Program of Outstanding Young Teachers of Hebei University of Chinese Medicine (No. YQ2018004) and Natural Science Foundation of Hebei Province (H2020423279).