STUDY OF THE INTERACTION BETWEEN QUERCETIN AND ASCORBIC ACID WITH MODEL MEMBRANES OF DIFFERENT LIPID COMPOSITION

Ascorbic acid (AA) and Quercetin (QUE) are bioactive compounds widely recognized by their potent antioxidant properties and have demonstrated efficacy in the treatment and prevention of various diseases, including cancer. Cancer is a disease that induces significant changes in the membranes of infected cells, the first barrier to be overcome by any bioactive compound when interacting with its target. Therefore, investigating the bioactive-membrane interaction can lead to an understanding of the mechanisms of action of these compounds, as well as their physicochemical relationships with the target environment. The objective of this research was to study the interaction between quercetin and ascorbic acid, both individually and in combination, with model membranes that mimic healthy (POPC/Chol 80:20) and cancerous cells (POPC/POPE/POPS/Chol 35:25:20:20) at pH 7.4 and 5.5, respectively. UV-Visible spectroscopy was used to determine the spectrophotometric properties of the bioactives, evaluate their affinities towards the membrane mimetics, and explore their potential detergent actions in the target systems. It was observed that the isolated and mixed bioactives interact with membrane mimetics in a distinct way. The QUE has greater affinity for the mimetic membranes of healthy cells in relation to cancerous ones. This result can be associated with its property of charge at acidic pH providing evidence that the anticancer activity of QUE is not dominated by electrostatic interactions. AA showed low affinity for both lipid bilayers, suggesting a mode of interaction distinct from QUE in relation to its anticancer potential, which is independent of the lipid composition and pH of the medium. In the mixture, the partition coefficient of QUE is reduced in both lipid compositions, suggesting that the presence of AA tends to modulate the QUE-membrane interaction. The turbidity results reinforce the differences between the interaction of AA and QUE with the model membranes. AA has a solubilizing effect of vesicles regardless of lipid composition while QUE induces aggregation of the healthy mimetic system. In the AA-QUE combination, the effect observed for QUE alone in each lipid composition predominates, being attenuated by the presence of AA.

This work was supported by Programa Institucional de Iniciação Científica e Tecnológica of Federal University of Triângulo Mineiro (UFTM) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG - APQ 00554-21).