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

<title>Abstract</title> <p> 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, <italic>Trametes versicolor</italic> laccase catalyzed their co-transformation under mild conditions (pH 4.5, 30°C), yielding five major products identified by UV-Vis and UHPLC-MS analysis. Three corresponded to oxidized quercetin derivatives and two to caffeic acid oxidation products, with the reaction displaying high selectivity toward quercetin (97% conversion) in comparison to caffeic acid (57%). 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 preserved cytotoxic effects against HeLa cells. Overall, although quercetin and caffeic acid have been extensively studied individually, this work demonstrates that laccase-catalyzed co-transformations generate novel phenolic derivatives with enhanced solubility and stability, providing a versatile platform for enzymatic generation of diverse phenolic combinations with potential functional applications. </p>