Síntese, caracterização e aplicação cosmética de derivados benzilados da quercetina

Abstract

The development of new molecules that can prevent damage resulting from skin aging is of great relevance for modern society as the population increasingly seeks a better physical appearance. Quercetin has many properties of interest for cosmetic application that aid in this prevention. The currently developed cosmetics seek to offer multiactivities. However, few studies have evaluated the effects of quercetin or derivatives for this purpose. Therefore, the present study had the objective of obtaining quercetin derivatives with various activities for cosmetic use. Initially, a synthesis was performed, by the substitution reaction between rutin and benzyl bromide (benzylation). After, the isolation was carried out by high performance liquid chromatography semipreparative, where two products of the reaction were obtained. By the characterization through mass spectrometry and nuclear magnetic resonance was possible the elucidation of the chemical structure of two quercetin derivatives, encoded as ACD32A and ACD32B. By DPPH, ABTS, and cell culture assays, the derivatives showed no antioxidant activity. In the in vitro glycation assay, the derivatives inhibited the formation of advanced glycation end products in collagen by the glyoxal pathway, with IC50 (μg/mL) of 12.18 ± 4.47 (ACD32A) and 21.27 ± 2,04 (ACD32B). The derivatives did not exhibit inhibitory activity against the enzymes elastase, hyaluronidase, and tyrosinase. In the cytotoxicity assay, by Alamar Blue method, the substances present low toxicity to human fibroblasts up to the concentration of 200 μg/mL. In the evaluation of the proliferative capacity and cellular migration of human fibroblasts, the derivatives demonstrated higher activity than the obtained by quercetin. In the inhibitory activity against collagenase, by zimographic method, the derivatives also exhibited inhibition of metalloproteinases better than quercetin. Finally, the partition coefficient and cutaneous permeability of the ACD32A and ACD32B were predicted in silico by the SwissADME server and the derivatives exhibited an increase in these coefficients, when compared to quercetin. The present study described for the first time the obtention of two benzylated substances of quercetin with various properties to be applied in cosmetics. Future studies will be needed to explore these applications in detail, as well as the mechanisms involved in the activities.