Characterization and functional evaluation of laccase-catalyzed synthesis of quercetin and caffeic acid derivatives

The applications of quercetin and caffeic acid are limited by poor aqueous solubility and chemical instability. Enzymatic catalysis offers a sustainable strategy to overcome these challenges. Thus, in this work, Trametes versicolor laccase catalyzed their co-transformation under mild conditions (pH 4.5, 30 °C), resulting in five major products identified by UV-Vis and UHPLC-MS analysis. Three corresponded to oxidized quercetin derivatives and two to caffeic acid oxidation products, indicating preferential transformation of quercetin, which converted to 97% compared with 57% caffeic acid. The combined reaction products (RP Q+CA ) exhibited improved aqueous solubility and maintained biological functionality. Despite a slight reduction in antioxidant activity (~ 20%), the products retained measurable cytotoxic activity against HeLa cells. Overall, although quercetin and caffeic acid have been extensively studied individually, our results demonstrate that their laccase-catalyzed co-transformation can generate phenolic derivatives with enhanced aqueous solubility and stability. This approach provides a versatile enzymatic platform for generating novel derivatives from phenolic compounds.