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Discovery of a Potential Anti-Ischemic Stroke Agent: 3-Pentylbenzo[ c ]thiophen-1(3 H )-one

2012; American Chemical Society; Volume: 55; Issue: 16 Linguagem: Inglês

10.1021/jm300681r

1520-4804

Jing Wu, Jingjing Ling, Xuliang Wang, Tingting Li, Jingchao Liu, Yisheng Lai, Hui Ji, Sixun Peng, Jide Tian, Yihua Zhang,

Free Radicals and Antioxidants

The development of novel antithrombotic agents with strong free radical scavenging activity is of great significance for the treatment of ischemic stroke. In the present study, 3-alkyl/arylalkyl-substituted benzo[c]thiophen-1(3H)-ones (5a-h) were designed and synthesized. The most active compound 5d significantly inhibited the adenosine diphosphate (ADP) induced and arachidonic acid (AA) induced in vitro platelet aggregation, superior to clinically used antiplatelet drug aspirin (ASP) and anti-ischemic stroke drugs 3-n-butylphthalide (NBP) and edaravone (Eda). More importantly, in comparison with both NBP and Eda, 5d exhibited stronger antithrombotic and free radical scavenging activities and better or comparable neuroprotective effects against ischemia/reperfusion (I/R) in rats by ameliorating neurobehavioral function, reducing infarct size and brain-water content, attenuating cerebral damage, and normalizing the levels of oxidative enzymes. Overall, our findings may provide an alternative strategy for the design of novel anti-ischemic stroke agents more potent than drugs like NBP and Eda.