title: Design, synthesis and biological evaluation of hydrogen sulfide releasing derivatives of 3-n-butylphthalide as potential antiplatelet and antithrombotic agents.
abstract: 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.
authors.affiliation: The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi 214122, P. R. China. jianyin@jiangnan.edu.cn.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Linna
authors.initials: L
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Sheng
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Huang
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Jinyi
authors.initials: J
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008297:Male; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis
chemical_list: D001572:Benzofurans; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; C027125:3-n-butylphthalide; D006862:Hydrogen Sulfide