Structural characteristics of flavanones and flavones from Cudrania tricuspidata for neuraminidase inhibition

The structural characteristics of flavonoids (1–3 and 6–8) from the root of Cudrania tricuspidata required for neuraminidase inhibition were studied and compared with commercially available flavonoids (4, 5, and 9–12). Alkylated flavanones (1–3) display better inhibition than the corresponding parent compound 4. Importantly, flavanone 1 bearing a C-8 hydrated prenyl group showed extremely high inhibition with IC50 of 380 nM. On the other hand, the parent flavone 5 was more effective than alkylated analogues (6–8). Isolated inhibitors (1–3 and 6–8) showed noncompetitive inhibition in kinetic studies. The binding affinity of flavanones (1–4) for neuraminidase in in silico docking experiments correlated well with their IC50 values and noncompetitive inhibition mode.

Graphical abstractStructure–activity relationship of flavonoids toward neuraminidase inhibition was investigated. Compound 1, which has a prenylhydrate substituent at the C8 position of flavanone, demonstrates potent activity against the neuraminidase.Figure optionsDownload full-size imageDownload as PowerPoint slide