Identification of Rutaecarpine-Pyridinium Quaternary Ammonium Conjugates Exhibiting Dual Mechanisms of Membrane-Targeting and DNA Topo I Inhibition as Potent Antimicrobials against Methicillin-Resistant Staphylococcus aureus

The structural diversity of natural products provides a major source for discovering antimicrobials with novel structures or mechanisms to overcome microbial resistance. Herein, we prepared a series of rutaecarpine-pyridinium quaternary ammonium conjugates by using rutaecarpine as the lead compound. Bioactivity evaluation demonstrated that <b>5dl</b> exhibits outstanding antibacterial activity against <i>S. aureus</i> ATCC 29213 and clinical MRSA isolates, with MIC values ranging from 0.5 to 2 μ