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.
Subject(s)
Animals , Humans , Male , Rabbits , Rats , Benzofurans , Chemistry , Hydrogen Sulfide , Chemistry , Molecular Structure , Nitric Oxide , Chemistry , Platelet Aggregation , Platelet Aggregation Inhibitors , Chemistry , Pharmacology , Rats, Sprague-Dawley , Thrombosis , Drug TherapyABSTRACT
Hydrogen sulfide (H2S) is considered as a new member of gasotransmitter family, following nitric oxide (NO) and carbon monoxide (CO). H2S exerts important biological effects in mammals, which has drawn more and more attention in recent years. It is proved that H2S has a role in the regulation of physiological and pathophysiological processes in the cardiovascular system and the nervous system. Several cardiovascular and nervous diseases are connected to H2S. H2S-releasing agents (also known as H2S donors) have been widely used not only as useful research tools but also potential therapeutic agents. In this review, we provide an overview of the chemistry and biology of H2S, and summarize the chemistry and biological activity of some natural and synthetic H2S donors. We introduce the developments of currently available H2S-releasing drugs including H2S-non-steroidal anti-inflammatory drugs, H2S-nervous system drugs and NO-H2S-releasing drugs. We hope this review will be a value reference in the development of H2S-releasing drugs in the treatment of cardiovascular and nervous diseases.