Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition

Pterocarpans (1–3) and flavanones (4–10) were isolated from Sophora flavescens and screened for their ability to inhibit neuraminidase (an enzyme crucial in the proliferation of the influenza virus). The majority of inhibitors were shown to have IC50 values of 20 μM or below. Interestingly, pterocarpan 1 emerged as the best inhibitor with an IC50 of 1.4 μM. We were thus able to prove that the pterocarpan skeleton is a new class of lead structure for neuraminidase inhibitors. Our studies reveal that the IC50 has a marked dependence upon structure in the case of the pterocarpans but much less so for the flavanones. Kinetic analysis disclosed that all inhibitors are noncompetitive. Our molecular docking experiment resulted that the most potent pterocarpan-derived inhibitor 1 may bind to another binding pocket adjacent to the active site.