Design, Synthesis, and Biological Activity of Thioguanine-Modified Pleuromutilin Derivatives.

Antibiotic overuse has caused the increasingly serious problem of bacterial drug resistance, with numerous marketed antibiotics exhibiting significantly reduced activity against drug-resistant bacteria. Therefore, there is urgent demand for the development of novel antibiotics. Pleuromutilin is a tricyclic diterpene exhibiting antibacterial activity against Gram-positive bacteria and is currently considered the most promising natural antibiotic. In this study, novel pleuromutilin derivatives were designed and synthesized by introducing thioguanine units, and their antibacterial activities against drug-resistant strains were evaluated and . Compound was observed to have a rapid bactericidal effect, low cytotoxicity, and potent antibacterial activity. The results suggest that has a significant therapeutic effect on local infections, and its activity is equal to that of retapamulin, an anti- pleuromutilin derivative.