title: Discovery of a potential anti-ischemic stroke agent: 3-pentylbenzo[c]thiophen-1(3H)-one.
abstract: 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.
authors: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors: Jing
authors: J
authors: Wu
authors: Jingjing
authors: J
authors: Ling
authors: Xuliang
authors: X
authors: Wang
authors: Tingting
authors: T
authors: Li
authors: Jingchao
authors: J
authors: Liu
authors: Yisheng
authors: Y
authors: Lai
authors: Hui
authors: H
authors: Ji
authors: Sixun
authors: S
authors: Peng
authors: Jide
authors: J
authors: Tian
authors: Yihua
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013237:Stereoisomerism; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C576402:3-pentylbenzo(c)thiophen-1(3H)-one; D000975:Antioxidants; D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes