Novel pleuromutilin derivatives conjugated with phenyl-sulfide and boron-containing moieties as potent antibacterial agents against antibiotic-resistant bacteria

In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b showed high stability in the liver microsomes of rats and humans, along with acceptable tolerance in vitro and in vivo. Additionally, compound 16b exhibited promising efficacy in MRSA-infected mouse models. Our data highlight the potential of conjugated pleuromutilin derivatives as valuable agents against drug-resistant bacteria. [Display omitted] •Novel pleuromutilin derivatives conjugated with phenyl-sulfide and boron-containing moieties were synthesized.•Conjugated derivatives showed potent activity against both susceptible and resistant Gram-positive bacteria.•Compound 16b displayed good stability and safety.•Compound 16b exhibited promising efficacy in MRSA-infected mouse models.