S-Alkylated sulfonium betulin derivatives: Synthesis, antibacterial activities, and wound healing applications

Betulin, a bioactive triterpenoid derived from Betulaceae bark with antimicrobial and anti-inflammatory properties, holds great potential as a therapeutic agent. In this work, cationic sulfonium-modified betulin derivatives were synthesized to enhance their antibacterial efficacy for wound healing application. Mono- and dual S-alkylated sulfonium derivatives significantly outperformed betulin in antibacterial activity against pathogens such as S. aureus, Methicillin-resistant S. aureus (MRSA), and E. coli. S-nonylated sulfonium betulin reduced the minimum inhibitory concentration of betulin against MRSA from 24 to 0.015 mM. The sulfonium modification enhanced cationic interactions, leading to bacterial membrane disruption. The derivatives expedited the process of wound healing by mitigating inflammation and exhibited satisfactory biosafety, proposing a viable approach to the development of antibacterial agents.