Melanogenesis acceleratory activity of synthesized quercetin derivatives and the structure activity relationships

Abstract

Melanogenic acceleratory effect of Helminthostachys zeylanica root extract was examined using murine B16 melanoma cells and the potent active compounds were identified. Two quercetin glycosides namely 4'-O-β-D-glucopyranosyl-quercetin-3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranoside 3, 4'-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-quercetin-3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranoside, and three ugonins, ugonin J, K, and L were isolated from H. zeylanica root extract by a series of chromatography. In order to elucidate the correlation of structure activity, ten quercetin glycosides included 3 and three quercetin derivatives were synthesized using rutin as a starting material. The identification of isolated compounds from H. zeylanica root extract and the synthesized quercetin glycosides were confirmed by NMR, MALDI or UPLC-TOFMS, IR, UV spectrum, and specific optical rotation. Among the quercetin glycosides, quercetin-3-O-β-D-glucopyranoside1, quercetin-3-O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranoside 2, and 3 showed intracellular melanogenesis acceleratory activity and 3-O-methylquercetin showed extracellular melanogenesis acceleratory activity in a dose dependent manner. These compounds showed no effect for the mushroom tyrosinase activity which catalyzes the rate limiting reaction of melanogenesis. Therefore they may have an effect on a gene expression relating to melanogenesis in melanoma cells.