title: Synthesis and biological evaluation of nitric oxide (NO)-hydrogen sulfide (H2S) releasing derivatives of (S)-3-n-butylphthalide as potential antiplatelet agents.
abstract: In the present study, a series of novel nitric oxide-hydrogen sulfide releasing derivatives of (S)-3-n-butylphthalide ((S)-NBP) were designed, synthesized, and evaluated as potential antiplatelet agents. Compound NOSH-NBP-5 displayed the strongest activity in inhibiting the arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation in vitro, with 3.8- and 7.0-fold more effectiveness than (S)-NBP, respectively. Furthermore, NOSH-NBP-5 could release moderate levels of NO and H2S, which would be beneficial in improving cardiovascular and cerebral circulation. Moreover, NOSH-NBP-5 could release (S)-NBP when incubated with rat brain homogenate. In conclusion, these findings may provide new insights into the development of novel antiplatelet agents for the treatment of thrombosis-related ischemic stroke.
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), School of Biotechnology, Jiangnan University, Wuxi 214122, China.
authors.forename: Zhao-Ya
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Wuxi People's Hospital, Wuxi 214023, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Ling
authors.affiliation: Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zyhtgd@163.com.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address: jianyin@jiangnan.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Yin
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry*; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry*; D008297:Male; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013927:Thrombosis / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D001572:Benzofurans; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; C027125:3-n-butylphthalide; D006862:Hydrogen Sulfide
keywords: (S)-3-n-butylphthalide; Antiplatelet agents; Hydrogen sulfide; Nitric oxide