Synthesis and biological evaluation of nitric oxide (NO)-hydrogen sulfide (HS) releasing derivatives of (S)-3-n-butylphthalide as potential antiplatelet agents.
10.1016/S1875-5364(17)30021-3
- Author:
Xiao-Li WANG
1
;
Zhao-Ya WANG
1
;
Jing-Jing LING
2
;
Yi-Hua ZHANG
3
;
Jian YIN
4
Author Information
1. Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), School of Biotechnology, Jiangnan University, Wuxi 214122, China.
2. Wuxi People's Hospital, Wuxi 214023, China.
3. Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zyhtgd@163.com.
4. Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), School of Biotechnology, Jiangnan University, Wuxi 214122, China. Electronic address: jianyin@jiangnan.edu.cn.
- Publication Type:Journal Article
- Keywords:
(S)-3-n-butylphthalide;
Antiplatelet agents;
Hydrogen sulfide;
Nitric oxide
- MeSH:
Animals;
Benzofurans;
chemistry;
Humans;
Hydrogen Sulfide;
chemistry;
Male;
Molecular Structure;
Nitric Oxide;
chemistry;
Platelet Aggregation;
drug effects;
Platelet Aggregation Inhibitors;
chemical synthesis;
chemistry;
pharmacology;
Rabbits;
Rats;
Rats, Sprague-Dawley;
Thrombosis;
drug therapy;
physiopathology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2016;14(12):946-953
- CountryChina
- Language:English
-
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 HS, 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.
