川芎嗪灯盏乙素苷元抗缺血性脑卒中孪药的合成及活性研究

Synthesis and biological evaluation of twin drug of tetramethylpyrazine and scutellarein for ischemic stroke

目的:设计合成川芎嗪灯盏乙素苷元孪药,研究其对于缺血性脑卒中的治疗作用。方法:以川芎嗪和灯盏乙素苷元为原药,通过共价键将其拼合,并对所合成目标化合物进行体外抗氧化损伤、抗凝血活性研究,筛选得到目标化合物4进行体内缺血再灌注损伤保护作用研究。结果:设计合成得到6个川芎嗪灯盏乙素苷元孪药,受试化合物均表现出良好的抗氧化损伤及抗凝血活性,化合物4高剂量组脑梗死体积比减小为23.7%(与模型组相比)。结论:孪药策略对于治疗缺血性脑卒中具有一定的参考价值。

Objective: To design and synthesize twin drug of tetramethylpyrazine and scutellarein for ischemic stroke. Methods: Based upon the theory of twin drug,six targeted compounds were synthesized and their structures were confirmed by 1H-NMR and HRMS. The antioxidant and anticoagulant activities of the target compounds were studied in vitro,and the selected compound was further evaluated for cerebral ischemia/reperfusion protection using middle cerebral artery occlusion (MCAO) model. Results: All the tested compounds showed good effect against oxidative damage and anticoagulant activity,and the volume ratio of cerebral infarction in the high dose group of compound 4 was reduced to 23. 7% compared with the MCAO group. Conclusion: The twin drug strategy has certain reference value for the treatment of ischemic stroke.