Three Australian Lepidosperma Labill. Species as sources of prenylated and oxyprenylated derivatives of piceatannol, resveratrol and pinosylvin: Melatoninergic binding and inhibition of quinone reductase 2

Abstract

Prenylated and hydroxyprenylated piceatannol, resveratrol and pinosylvin derivatives were isolated from resin produced by three Australian Lepidosperma Labill. Species (Cyperaceae). From L. congestum R.Br. one known compound, 3',5'-bis-prenyl-E-resveratrol, and five undescribed compounds were isolated, 3'-O-prenyl-5'-prenyl-E-piceatannol, 5',6'-bis-prenyl-E-piceatannol, 5'-prenyl-E-piceatannol, 3',5'-bis(3-hydroxy-3-methylbutyl)-E-resveratrol and 3',5'-bis-E-hydroxyprenyl-E-resveratrol. From L. gunnii Boeckeler one undescribed compound was isolated, 3'-E-hydroxyprenyl-5'-Z-hydroxyprenyl-E-resveratrol. From L. laterale R.Br. six undescribed compounds were isolated, 3-O-prenyl-E-pinosylvin, 3-O-Z-hydroxyprenyl-E-pinosylvin, 3'-Z-hydroxyprenyl-E-resveratrol, 3-O-Z-hydroxyprenyl-E-resveratrol, 3-O-Z-hydroxyprenyl-4'-O-methyl-E-resveratrol, and 3-O-prenyl-3'-δ,δ'-dihydroxyprenyl-E-resveratrol. Compounds, including a reference compound 3-O-prenyl-3'-O-methyl-E-piceatannol, were screened in an assay for melatoninergic binding to MT1 and MT2 receptors and binding to QR2/MT3 enzyme, and for inhibition of QR2/MT3 in a functional assay. Strong binding was observed for 3-O-Z-hydroxyprenyl-E-resveratrol with a K_i of 0.022 nM and the strongest inhibition of QR2/MT3 observed was for the reference compound, 3-O-prenyl-3'-O-methyl-E-piceatannol, with an inhibition of 61% at 1 μM and 95% at 10 μM. The three most active binders and inhibitors of QR2/MT3 were found to have a common substructure corresponding to 3-O-prenylresveratrol.

Keywords: Cyperaceae; L. gunnii; L. laterale; Lepidosperma congestum; Melatonin receptors; Oxyprenylation; Piceatannol; Prenylation; Quinone reductase 2 inhibitors; Resveratrol.