Design and synthesis of coumarin-based amphoteric antimicrobials with biofilm interference and immunoregulation effects

Abstract

Bacterial infections pose a threat to human and animal health, and the formation of biofilm exacerbates the microbial threat. New antimicrobial agents to address this challenge are much needed. In this study, several new amphoteric compounds derived from the natural product coumarin were designed and synthesized by mimicking the structure and function of antimicrobial peptides. Strong inhibitory effect of 8b was observed on S. aureus 29213 and five isolated clinically positive strains, with an MIC value of 1–4 μg mL⁻¹, accompanied by the potential advantages of rapid sterilization and no drug resistance. The in vivo activity of 8b was supported by good antibacterial and anti-inflammatory effects in a mouse wound infection model. More importantly, good immunomodulatory effects, inhibition of biofilm formation, and biofilm clearance were detected in the treatment using 8b, which makes it a potential candidate antibacterial for controlling S. aureus infections forming biofilm.