RESUMO
Accessible triterpenoids of ursane and lupane series, the flavonoid dihydroquercetin and their synthetic derivatives with polar substituentss were tested in vitro for inhibition of collagenase 1 (MMP-1) in UVB irradiation assay. Ursolic acid and uvaol disuccinate were the most active inhibitors in the ursane series. In the lupane series, the best inhibition was manifested by carboxymethyl ester of betulonic acid and betulin succinates. Down- regulation of MMP-1 by dihydroquercetin and its synthetic derivatives surpassed the activity of a standard (retinoic acid).
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Quercetina/análogos & derivados , Envelhecimento da Pele/efeitos dos fármacos , Triterpenos/farmacologia , Anti-Inflamatórios não Esteroides/química , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Humanos , Interleucina-8/antagonistas & inibidores , Queratinócitos/efeitos dos fármacos , Metaloproteinase 1 da Matriz , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Quercetina/química , Quercetina/farmacologia , Tretinoína/química , Tretinoína/farmacologia , Triterpenos/química , Raios Ultravioleta , Ácido UrsólicoRESUMO
Aldose reductase (AR) is the first enzyme in the polyol pathway. AR has been reported to play an important role in the pathogenesis of diabetic complications. Ursolic acid and fourteen synthetic derivatives with ursane skeleton were tested for recombinant human aldose reductase (rhAR) inhibitory activity for development of diabetic complications. Among them, N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) showed most potent rhAR inhibitory activity in vitro. Inhibition mode of N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid (XV) was tested uncompetitively by kinetic analysis using the Lineweaver-Burk plots. Ursolic acid derivative N-(3beta-hydroxyurs-12-en-28-oyl)-4-aminobutyric acid is able to inhibit rhAR uncompetitively and could be offered as a lead compound for AR inhibition.
