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

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 '-prenylE-piceatannol, 5 ',6 '-bis-prenyl-E-piceatannol, 5 '-prenyl-E-piceatannol, 3 ',5 '-bis(3-hydroxy-3-methylbutyl)-Eresveratrol 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, 3O-Z-hydroxyprenyl-E-resveratrol, 3-O-Z-hydroxyprenyl-4 '-O-methyl-E-resveratrol, and 3-O-prenyl-3 ' 8,8 '-dihydroxyprenyl-E-resveratrol. Compounds, including a reference compound 3-O-prenyl-3 '-O-methyl-Epiceatannol, 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-Zhydroxyprenyl-E-resveratrol with a Ki 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 mu M and 95% at 10 mu M. The three most active binders and inhibitors of QR2/MT3 were found to have a common substructure corresponding to 3-O-prenylresveratrol.

Automated summary

A series of prenylated and hydroxyprenylated compounds were isolated from resin produced by certain Australian plants, showing strong binding affinity and inhibition activity towards melatonin receptors and enzymes.