Wang Xiaoli, Wang Linna, Sheng Xiao, Huang Zhangjian, Li Tingting, Zhang Ming, Xu Jinyi, Ji Hui, Yin Jian, Zhang Yihua
The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi 214122, P. R. China.
Org Biomol Chem. 2014 Aug 21;12(31):5995-6004. doi: 10.1039/c4ob00830h.
In the present study, a series of hydrogen sulfide (H2S) releasing derivatives (8a–g and 9a–f) of 3-n-butylphthalide (NBP) were designed, synthesized and biologically evaluated. The most promising compound 8e significantly inhibited the adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation in vitro, superior to NBP, ticlopidine hydrochloride and aspirin. Furthermore, 8e could slowly produce moderate levels of H2S in vitro, which could be beneficial for improving cardiovascular and cerebral circulation. Most importantly, 8e protected against the collagen and adrenaline induced thrombosis in mice, and exhibited greater antithrombotic activity than NBP and aspirin in rats. Overall, 8e could warrant further investigation for the treatment of thrombosis-related ischemic stroke.
在本研究中，设计、合成并对一系列3-正丁基苯酞（NBP）的硫化氢（H₂S）释放衍生物（8a–g和9a–f）进行了生物学评价。最有前景的化合物8e在体外能显著抑制二磷酸腺苷（ADP）和花生四烯酸（AA）诱导的血小板聚集，优于NBP、盐酸噻氯匹定和阿司匹林。此外，8e在体外能缓慢产生适度水平的H₂S，这可能有利于改善心血管和脑循环。最重要的是，8e可预防小鼠胶原和肾上腺素诱导的血栓形成，且在大鼠中表现出比NBP和阿司匹林更强的抗血栓活性。总体而言，8e值得进一步研究用于治疗血栓相关的缺血性中风。
