Center of Drug Discovery, China Pharmaceutical University, Nanjing, P R China.
Org Biomol Chem. 2011 Aug 21;9(16):5670-81. doi: 10.1039/c1ob05478c. Epub 2011 Jun 24.
Novel nitric oxide (NO) releasing derivatives (7a-7l) of 3-n-butylphthalide (NBP) were designed and synthesized. Compound 7e inhibited the adenosine diphosphate (ADP), thrombin (TH) and arachidonic acid (AA)-induced in vitro platelet aggregation, superior to NBP and aspirin, released moderate levels of NO, and improved aqueous solubility relative to NBP. Furthermore, 7e exhibited greater antithrombotic activity than NBP and aspirin in rats, and protected against collagen and adrenaline-induced thrombosis in mice. Therefore, NO-releasing NBP derivatives possessed potent antiplatelet aggregation and antithrombotic activity. Our findings may aid in the design of new therapeutic agents for the treatment of thrombosis-related ischemic stroke.
新型一氧化氮（NO）释放衍生物（7a-7l）被设计和合成。化合物 7e 抑制了体外血小板聚集的二磷酸腺苷（ADP）、凝血酶（TH）和花生四烯酸（AA）诱导，优于丁基苯酞（NBP）和阿司匹林，释放出中等水平的一氧化氮，且相对于 NBP 提高了水溶解度。此外，7e 在大鼠中表现出比 NBP 和阿司匹林更强的抗血栓形成活性，并能预防胶原和肾上腺素诱导的小鼠血栓形成。因此，NO 释放的 NBP 衍生物具有强大的抗血小板聚集和抗血栓形成活性。我们的发现可能有助于设计治疗与血栓形成相关的缺血性中风的新型治疗剂。
