Synthesis and biological evaluation of nitric oxide (NO)-hydrogen sulfide (H2S) releasing derivatives of (S)-3-n-butylphthalide as potential antiplatelet agents

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)- an...

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Bibliographic Details
Published in:Chinese journal of natural medicines 2016-12, Vol.14 (12), p.946-953
Main Authors: WANG, Xiao-Li, WANG, Zhao-Ya, LING, Jing-Jing, ZHANG, Yi-Hua, YIN, Jian
Format: Article
Language:English
Subjects:
(S)-3-n-butylphthalide
Animals
Antiplatelet agents
Benzofurans - chemistry
Humans
Hydrogen sulfide
Hydrogen Sulfide - chemistry
Male
Molecular Structure
Nitric oxide
Nitric Oxide - chemistry
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - chemical synthesis
Platelet Aggregation Inhibitors - chemistry
Platelet Aggregation Inhibitors - pharmacology
Rabbits
Rats
Rats, Sprague-Dawley
Thrombosis - drug therapy
Thrombosis - physiopathology
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Summary: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.
ISSN:1875-5364
1875-5364
DOI:10.1016/S1875-5364(17)30021-3