Neurotoxicity and Structure-Activity Relationships of Resveratrol and its two Natural Analogs, 4,4′-Dihydroxystilbene and Pinosylvin

Abstract

Resveratrol (RES) and its two natural analogues, 4,4′-dihydroxystilbene (DHS) and pinosylvin (PIN), are very important polyphenols and have attracted considerable pharmaceutical interest because of their diverse biological activities. However, their adverse effects on motor nerves and glioma cells have not been properly assessed. Herein, we surveyed the toxicity and analyzed the structure-activity relationship of these three polyphenols using transgenic zebrafish ( Danio rerio) and U87. Results indicated that, in zebrafish embryos, both DHS (1 and 10 μg/mL) with hydroxyl groups at the 4 and 4′ positions, and PIN (1 and 10 μg/mL) with hydroxyl groups at the 3 and 5 positions inhibited motor neuron growth more effectively than RES (1 and 10 μg/mL) with hydroxyl groups at the 3, 4′, and 5 positions, although their appearance is normal. Both the DHS- (10 μg/mL) and PIN (10 μg/mL) -treated groups significantly reduced the swimming distance of zebrafish compared with the RES (10 μg/mL) -treated group. In addition, DHS with the hydroxyl groups at the 4 and 4′ positions (0.002, 0.02, 0.2, 2, and 20 μM) inhibited U87 cell aggregation in a concentration-dependent manner; PIN with the hydroxyl groups at the 3 and 5 positions (0.002, 0.02, 0.2, 2, and 20 μM) promoted U87 cell aggregation in a concentration-dependent manner, while RES with three hydroxyl groups promoted U87 cell aggregation at concentrations from 0.2 to 2 μM. Taken together, DHS and PIN are more neurotoxic than RES. The position and number of hydroxyl groups significantly affected the ability of the polyphenols to aggregate into tumors in the U87 cell.

Iridium-Catalyzed Ligand-Controlled Semi-Reduction of Alkynes Employing H2O as the Hydrogen Donor and Its Application

“…proach in a practical application, we studied the drug effects of its analogue 3k [(E)-1,3-dimethoxy-5-styrylbenzene] in accordance with a previous report. 10 The test results showed that treatment of zebrafish embryos with 3k (0.01-1 g/mL) led to a significant neurosuppressive effect (Figure 1), suggesting that 3k might be developed as a potential nerve-growth inhibitor. Additional experiments were performed to gain insight into the reaction mechanism.…”

“…We then screened a range of reaction temperatures to identify the optimal temperature. Control experiments showed that when the reaction temperature reached 120 °C, the conversion rate of the alkyne reached 100%, and when the reaction temperature was below 120 °C, the conversion rate was lower (entries [10][11][12]. These results show that 120 °C is the optimal temperature.…”