Enzymatic modification of dihydromyricetin by glucosylation and acylation, and its effect on the solubility and antioxidant activity

Abstract

Although dihydromyricetin exhibits strong potential for pharmaceutical applications, its limited aqueous solubility, permeability and stability restrict its use. In this work, we have synthesized a series of glucosides and acyl-glucosides of dihydromyricetin that could increase the bioavailability of this molecule. First, the R134A variant of sucrose phosphorylase from Thermoanaerobacterium thermosaccharolyticum catalyzed the formation of three monoglucosides, and the major one was identified as dihydromyricetin 4′-O-α-D-glucopyranoside (>75% conversion yield). The molecular features that define this specificity for the 4′-OH phenolic group were investigated through induced-fit docking analysis of each potential derivative. Furthermore, the acylation of the 4′-monoglucoside with fatty acid vinyl esters (C8, C12, and C16) was performed with high efficiency using the lipase from Thermomyces lanuginosus. Three novel acyl derivatives of dihydromyricetin were characterized. Furthermore, the water solubility and antioxidant activity (ABTS, DPPH) of the synthesized compounds were measured, concluding that the location of the glucosyl moiety may affect their physicochemical properties and, as a result, their bioactivity.