Potential Anti‐hyperuricemic Agents from Proanthocyanidins, Procyanidins, and Benzophenone Glucosides via In Silico Docking Analysis Verified with In Vitro Bioassay

In a continuation of searching natural xanthine oxidase inhibitors as anti‐hyperuricemic agent, in silico virtual screening of epicatechin (1) and A‐type proanthocyanidins 2–8, isolated from Machilus philippinensis , by molecular docking was undertaken and subsequent in vitro assay was followed. The bioassay result correlated well with the docking score. Additional A‐type proanthocyanidins 9–16 and procyanidins 17 & 18, present in peanut skin, were isolated and assayed against XO. Although their inhibitory activities were low but correlated well with the docking scores, too. This study indicated in silico virtual docking to be applicable to predict the XO inhibitory activity for proanthocyanidins with the molecular weight ranging from dimers (MW∼550) to hexamers (MW∼1750). For verifying such virtual screening to other phenolics, this approach was extended to benzophenone glucosides 19–22, isolated from Planchonella obovata . Likewise their inhibitory activities against XO correlated well with the docking score. Of these 22 compounds, the tetramer 5, pentamer 7, hexamer 8, and the digalloylated 22, having the docking score around −25.5 Kcal/mol, showed comparable inhibitory activity against xanthine oxidase to allopurinol (IC50∼40.0 vs. 58.5 μM). Further application of such virtual screening on XO template will keep going for searching potential anti‐hyperuricemic drugs. This study demonstrates the docking score from in silico virtual screening of natural xanthine oxidase inhibitors correlated well with in vitro assay. Among 15 A‐type proanthocyanidins (2–16) and four benzophenones (19–22), the tetramer 5, pentamer 7, hexamer 8, and the digalloylated 22, having the docking score (ΔG) around −25.5 Kcal/mol, showed comparable inhibitory activity against xanthine oxidase to allopurinol (IC50∼40.0 vs. 58.5 μM).