Design, Synthesis, Antibacterial Activity, and Mechanism of Action of Coumarin Derivatives Containing Benzylamine

ABSTRACT A series of novel coumarin derivatives were synthesized by successfully combining the coumarin backbone with benzylamine groups using active splicing technology and chemical synthesis. These derivatives demonstrated excellent antibacterial activity in vitro, with compound A5 being particularly prominent. Through three‐dimensional quantitative structure–activity relationships (3D‐QSAR) analysis, it was found that the introduction of an electron‐donating group at the R1 position and a larger group at the R2 position could enhance the antibacterial activity, and the action mechanism of compound A5 was studied. The experimental results showed that A5 could increase the permeability of the bacterial membrane, thus disrupting the Xoo membrane and effectively inhibiting bacterial growth. This finding not only reveals the antibacterial mechanism of A5, but also provides an important scientific basis for the development of new antibacterial agents.