Abstract
In search of novel anti-ischemic stroke agents with higher potency than a known drug 3-n-butylphthalide (NBP), a series of hybrids ((S)- and (R)-5a-f) from optically active ring-opened NBP derivative and isosorbide were synthesized for evaluating their anti-ischemic stroke activity. Compound (S)-5e displayed the strongest activity in inhibiting the adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation in vitro, with 10.0- and 8.4-fold more effectiveness than (S)-NBP, respectively. Furthermore, (S)-5e was stable in artificial gastrointestinal fluids and could penetrate the blood-brain barrier (BBB) with an appreciate lipid/water partition coefficient relative to (S)-NBP. More importantly, oral treatment with (S)-5e protected from acute thrombosis and inhibited the ischemia/reperfusion-related brain injury in animals. Our findings suggest that (S)-5e may be promising for further evaluation for the intervention of ischemic stroke.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.