Systematic identification of bacterial neuraminidase inhibitors from Psoralea corylifolia using ultrafiltration-UPLC-Q-Orbitrap-MS and molecular dynamics.

Bacterial neuraminidase (BNA) is a potential target for discovering anti-infective agents. Here, the BNA inhibitory activity of the ethanolic extract of Psoralea corylifolia (EEPC) was investigated using integrated experimental and computational approaches. Affinity ultrafiltration-UPLC-Q-Orbitrap-MS prioritised 11 representative constituents as putative BNA-interacting compounds. Five compounds (7-11) inhibited BNA with IC50 values of 4.67-34.09 μM. Bakuchiol (11) exhibited the strongest activity (IC50 = 4.67 ± 0.26 μM), and compounds 7, 9, and 10 were more active than the positive control, quercetin (IC50 = 13.63 ± 1.05 μM). Kinetic analysis indicated that bakuchiol (11) was competitive, whereas compounds 7-10 showed mixed-type inhibition. Docking and molecular dynamics analyses suggested that bakuchiol (11) and 3-hydroxybakuchiol (10) may form relatively stable BNA complexes. In silico absorption, distribution, metabolism, excretion, and toxicity analysis further supported bakuchiol (11) as a promising lead candidate among the tested compounds.