Selective Synthesis and Biological Evaluation of Sulfate-Conjugated Resveratrol Metabolites

Abstract

Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF)-α-induced NFκB activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide production in endotoxin-stimulated macrophages, and proliferation of KB or MCF7 cells, induction of quinone reductase 1 (QR1), accumulation in the sub-G 1 phase of the cell cycle, and quenching of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. Two metabolites showed activity in these assays; the 3-sulfate exhibited QR1 induction, DPPH free radical scavenging, and COX-1 and COX-2 inhibitory activities, and the 4′-sulfate inhibited NFκB induction, as well as COX-1 and COX-2 activities. Resveratrol, as well as its 3′-sulfate and 4-sulfate, inhibit NO production by NO scavenging and down-regulation of iNOS expression in RAW 264.7 cells. Resveratrol sulfates displayed low antiproliferative activity and negligible uptake in MCF7 cells.

Endophytic fungi associated withTaxus fuana(West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents

“…Data were calculated as % inhibition relatively to DMSO control. Samples which showed more than 60% inhibition at the test concentration 20 lg/mL were tested for dose-dependence to determine IC 50 values (Hoshino et al 2010). Three NFjB inhibitors were used as positive controls: N-tosyl-L-phenylalanylchloromethyl ketone (TPCK), IC 50 ¼ 3.8 ± 0.6 lM; (E)-3-(4-methylphenylsulfonyl)-2-propenenenitrile (BAY-11), IC 50 ¼ 2.0 ± 0.33 lM; resveratrol, IC 50 ¼ 2.5 ± 0.3 lM.…”

Biological activity and mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulphated derivatives

“…Проведенная нами серия биологических испытаний сульфатированного конъюгата ЛТ -ДСЛ показала, что он проявляет большую лечебную активность, чем ЛТ при моделировании СД2 и гиперлипидемии [47]. Можно предположить, что подобно ресвератролу сульфатированный ЛТ более эффективно всасывается эпителиальными клетками, чем чистый ЛТ [47].…”

“…Можно предположить, что подобно ресвератролу сульфатированный ЛТ более эффективно всасывается эпителиальными клетками, чем чистый ЛТ [47]. Нельзя исключать и того, что сульфатированные конъюгаты ЛТ, подобно эстрон сульфату [48], служат неактивным пулом этого флавона, а при гидролизе сульфатазами достигают клеток-мишеней.…”

Anticancer Activities of Resveratrol in Colorectal Cancer

“…Another study evaluated the biological activities of five resveratrol sulfate metabolites in several in vitro assay systems. Even though two of these metabolites showed induction of NADPH:quinone oxidoreductase 1 (NQO1), inhibition of COX-1 and COX-2, and decrease in NO production in a cell-free system, cellular uptake of these resveratrol metabolites was insignificant in vitro [49]. A large study, also using various in vitro assays, tested 92 resveratrol derivatives and reported that several metabolites had activities that were even more potent than the parent compound in specific assays.…”