Tyrosinase and 5α-Reductase Inhibitory Components from Artocarpus incisus Tree

Abstract

The inhibitory components on tyrosinase and 5 a reductase from Papua New Guinean (PNG) and Thai woody plants were investigated . First, the inhibitory components of Artocarpus incisus heartwood which showed the strongest inhibitory activity in 23 PNG wood species, their structureactivity relationships and inhibitory mechanism were evaluated. Tyrosinase inhibitory activityguided fractionation led to the isolation of seven active compounds including two new compounds, 3,2' , 4'trihydroxy , 6dimethylpyrano(3 , 2 :4,5 ) trans stilbene (artocarbene) and 6 (3methyl-1 butenyl) -5,7,2' , 4'-tetrahydroxyflavone ( isoartocarpesin) . The structure-activity relation ships suggested that specific natural or synthesized compounds having 4substituted resorcinol skeleton had potent tyrosinase inhibitory ability. Kinetic studies have indicated that specific compounds having 4substituted resorcinol skeleton exhibit competitive inhibition of the oxida tion of DL-DOPA by mushroom tyrosinase. Second, 5 a reductase inhibitory components from PNG and Thai plants were investigated respectively , and their structureactivity relationships were discussed . The methanol extract of heartwood of A. incisus showed potent 5 a reductase inhibitory activity. Chlorophorin and artocarpin showed more potent inhibitory effects (ICso 37 u M and 85 u M , respectively) than did a linolenic acid , which is known as a naturally occurring potent inhibitor. The inhibitory effects of 17 samples prepared from Thai plants on 5 a reductase activity were examined. The acetone extract of A. incisus leaves showed potent 5 a reductase inhibitory activity. Fractionation guided by 5 a reductase inhibitory test led to the isolation of 2-geranyl-2', 3,4, 4'tetrahydroxydihydrochalcone (IC 38 it M) and a novel geranylated chalcone, 3'-ger anyl-2' , 3 , 4 , 4'tetrahydroxychalcone (IC 104 u M) from the acetone extract of A. incisus leaves. Structureactivity relationship suggested that the presence of an isoprenederived sub stituent (prenyl and geranyl) would enhance 5 a reductase inhibitory effects.