Validation of in Silico Docking Analysis of Oligophenylpropanoids to Xanthine Oxidase by Correlation with in Vitro Bioassay and Its Application to Phlorotannins

The oligo-phenylpropanoids 1−7, isolated from Hyptis rhombodes, have been found to possess potent inhibitory activity against xanthine oxidase (EC 1.2.3.2, bovine milk). To rationalize such activity, computer assisted docking of these compounds and allopurinol, a positive control, on the xanthine oxidase was undertaken in this study. The docking scores, obtained by London (trimatch)−refinement (Forcefield Affinity ΔG) mode, showed good correlation with the IC50 values. That the compounds possessing 7′-Z configuration had much better inhibitory activity than those 7′-E isomers is well rationalized by this docking study. Virtual screening of eight phlorotannins (8−15) by this refinement mode found good docking scores. The bioassay result of three available ones (9, 12, 13) also indicated the consistency with the docking scores. While refined by Forcefield−London mode, certain inconsistency among the docking score and bioassay result was observed on either phenylpropanoid oligomers or three phlorotannins. Hence the London (trimatch)−refinement (Forcefield−Affinity ΔG) mode is recommended for virtual screening of the related phenolics. Three phlorotannins (11, 14, 15) were found to have better docking score than 6,6'-bieckol (12) and dieckol (13), both showing comparable inhibitory activity against xanthine oxidase to allopurinol, and thus they deserve further study. In addition, as these phlorotannins are rich in the Ecklonia genus, the common edible seaweeds such as E. cava and E. stolonifera are demonstrated to be beneficial to hyperuricemic patients.