Pharmacokinetic Prediction and Cytotoxicity of New Quercetin Derivatives

Quercetin (QUE) possesses various pharmacological properties; however, its low bioavailability and solubility hinder its beneficial effects. Enzymatic glycosylation has been explored to improve these aspects. In the present study, we used a sucrose phosphorylase variant to catalyze the regioselective transglucosylation of QUE, predicted the pharmacokinetic properties and toxicity of these molecules using in silico tools, and evaluated their cytotoxicity compared to the original molecule and a β-glucosylated derivative of QUE. Three α-glucosylated derivatives were obtained, which demonstrated improved pharmacokinetics, including a higher volume of distribution and lower clearance rate, with minimal likelihood of cytochrome P450 enzyme inhibition compared to QUE. QUE and the β-glucosylated derivative exhibited cytotoxicity in both cell types evaluated, whereas their α-glucosylated derivatives were nontoxic. The results presented provide an insight into the predicted behavior of these molecules in the body and, combined with cytotoxicity evaluation, will serve as a foundation for investigating the biological effects and mechanisms of action of these new molecules.