Novel multi-functional nitrones for treatment of ischemic stroke

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• 作者：Yewei Sun ; Gaoxiao Zhang ; Zaijun Zhang ; Pei Yu ; Haijing Zhong ; Jing Du ; Yuqiang Wang ; ^{yuqiangwang2001@yahoo.com}
• 关键词：YTODWFWUZZDJQX-RIYZIHGNSA-N ; SBEIXKZEOGRZBC-LQGKIZFRSA-N ; ZWTPGNRVKJOGJE-UHFFFAOYSA-N ; WELYTQPQVYNICP-CXUHLZMHSA-N ; QGUXKOQDVGSPGU-CXUHLZMHSA-N ; GZZXSIINAWMBBU-OQLLNIDSSA-N
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 June, 2012
• 卷：20
• 期：12
• 页码：3939-3945
• 文件大小：901 K

摘要

Ischemic stroke resulting from obstruction of blood vessels is an enormous public health problem with urgent need for effective therapy. The co-administration of thrombolytic/antiplatelet agent and neuroprotective agent improves therapeutic efficacy and agent possessing both thrombolytic/antiplatelet and antiradical activities provides a promising strategy for the treatment of ischemic stroke. We have previously reported a novel compound, namely TBN, possessing both antiplatelet and antiradical activities, showed significant neuroprotective effect in a rat stroke model. We herein report synthesis of a series of new pyrazine derivatives, and evaluation of their biological activities. Their mechanisms of action were also investigated. Among these new derivatives, compound 21, armed with two nitrone moieties, showed the greatest neuroprotective effects in vitro and in vivo. Compound 21 significantly inhibited ADP-induced platelet aggregation. In a cell free antiradical assay, compound 21 was the most effective agent in scavenging the three most damaging radicals, namely ^{OH, and ONOO鈭?/sup>.}