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

作　　者：ZHANG Yin-Qiu WU Jian-Bing YIN Wei ZHANG Yi-Hua HUANG Zhang-Jian 

机构地区：[1]State Key Laboratory of Natural Medicines,Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases,Center of Drug Discovery,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Chinese Journal of Natural Medicines》2020年第8期633-640,共8页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81822041;81773573;21977116;and 81673305);the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2018ZX09711002-006-013);the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMZZCX201824);the State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(No.SKL-HIDCA-2018-1);part of the work was supported by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX18_0795)。

摘　　要：To search for potent anti-ischemic stroke agents,a series of tetramethylpyrazine(TMP)/resveratrol(RES)hybrids 6 a-t were designed and synthesized.These hybrids inhibited adenosine diphosphate(ADP)-or arachidonic acid(AA)-induced platelet aggregation,among them,6 d,6 g-i,6 o and 6 q were more active than TMP.The most active compound 6 h exhibited more potent antiplatelet aggregation activity than TMP,RES,as well as positive control ticlopidine(Ticlid)and aspirin(ASP).Furthermore,6 h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide(H2 O2)or hydroxyl radical(·OH).Importantly,6 h 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 6 h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.

关 键 词：LIGUSTRAZINE RESVERATROL HYBRIDS Anti-platelet aggregation ANTIOXIDANT Ischemic stroke 

分 类 号：R914.5[医药卫生—药物化学] R965[医药卫生—药学]