Polyynes from Notopterygium incisum: Targeting bacterial cell membranes as a strategy against methicillin-resistant...

The emergence of bacterial resistance poses significant challenges to the effective treatment of bacterial infections. This underscores the urgent need to develop novel and effective drugs to combat bacterial infections. Pharmaceutical plants are rich in diverse natural compounds and represent a valuable source for the discovery of novel antimicrobial agents. Herein, we isolated ten polyyne compounds from Notopterygium incisum, including five previously unreported compounds. Their planar structures were confirmed by NMR and HRESIMS, and their absolute configurations were determined by matching DFT theoretical calculations with experimental results. In vitro studies indicate that compound 1 exhibits potent antibacterial activity against MRSA, with low resistance and effective biofilm eradication properties. Further investigation into the antibacterial mechanism reveals that compound 1 can cause bacterial death by disrupting the bacterial membrane, leading to ATP leakage and the generation of ROS. In vivo studies have demonstrated that compound 1 significantly ameliorates wound infection, reduces inflammatory levels, and promotes wound healing. Our discoveries suggest the potential application of compound 1 as an antibacterial agent for treating MRSA infections.