RESUMEN
We investigated the ability of polyphenol fatty acid esters to inhibit the activity of serine proteases trypsin, thrombin, elastase and urokinase. Potent protease inhibition in micromolar range was displayed by rutin and rutin derivatives esterified with medium and long chain, mono- and polyunsaturated fatty acids (1e-m), followed by phloridzin and esculin esters with medium and long fatty acid chain length (2a-d, 3a-d), while unmodified compounds showed only little or no effect. QSAR study of the compounds tested provided the most significant parameters for individual inhibition activities, i.e. number of hydrogen bond donors for urokinase, molecular volume for thrombin, and solvation energy for elastase. According to the statistical analysis, the action of elastase inhibitors is opposed to those of urokinase and thrombin. Cluster analysis showed two groups of compounds: original polyphenols together with rutin esters with short fatty acid chain length and rutin esters with long fatty acid chain length.
Asunto(s)
Ácidos Grasos/química , Elastasa Pancreática/antagonistas & inhibidores , Relación Estructura-Actividad Cuantitativa , Inhibidores de Serina Proteinasa/química , Trombina/antagonistas & inhibidores , Tripsina/química , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidores , Animales , Candida/química , Candida/enzimología , Bovinos , Esculina/química , Ésteres , Proteínas Fúngicas/química , Enlace de Hidrógeno , Cinética , Lipasa/química , Simulación del Acoplamiento Molecular , Páncreas/química , Páncreas/enzimología , Florizina/química , Teoría Cuántica , Rutina/química , Inhibidores de Serina Proteinasa/síntesis química , Especificidad por Sustrato , PorcinosRESUMEN
Quercetin is a natural polyphenol with proven health beneficial activities. In this study 15 new quercetin derivatives were prepared with the aim to enhance their bioavailability. Modification of their physicochemical properties could herewith improve the action in cells. The prepared compounds were tested for their antioxidant and cytotoxic activity. The ability to scavenge free radicals as well as ferric reducing antioxidant power of the new derivatives was not better than that of unmodified quercetin. But for acetylated esters a better cytotoxic activity was found on human cervical cancer cells HeLa than for the initial molecule. The best effect revealed chloronaphtoquinone quercetin (IC50=13.2 µM). For this compound comparable cytotoxic action on non-cancer murine fibroblast cells was detected (IC50=16.5 µM). The obtained results indicate that appropriate lipophilization of the quercetin molecule could improve its cytotoxic action in cells, probably due to its enhanced bioavailability.