Chinese Journal of Natural Medicines (English Ed.) 2020;18(8):633-640

doi:10.1016/S1875-5364(20)30076-5

Design, synthesis, and biological evaluation of ligustrazine/resveratrol hybrids as potential anti-ischemic stroke agents.

Yin-Qiu ZHANG 1 ; Jian-Bing WU 1 ; Wei YIN 1 ; Yi-Hua ZHANG 2 3 ; Zhang-Jian HUANG 4

Affiliations

+expand

Keywords

Anti-platelet aggregation; Antioxidant; Hybrids; Ischemic stroke; Ligustrazine; Resveratrol

Country

China

Language

English

Abstract

To search for potent anti-ischemic stroke agents, a series of tetramethylpyrazine (TMP)/resveratrol (RES) hybrids 6a-t were designed and synthesized. These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, 6d, 6g-i, 6o and 6q were more active than TMP. The most active compound 6h exhibited more potent anti-platelet aggregation activity than TMP, RES, as well as positive control ticlopidine (Ticlid) and aspirin (ASP). Furthermore, 6h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide (HO) or hydroxyl radical (·OH). Importantly, 6h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation (OGD/R) injury, comparable to an anti-ischemic drug edaravone (Eda). Together, our findings suggest that 6h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.