Design, Synthesis of 3-n-Butylphthalide-Hydrazine/Hydrazide Derivatives as Potential Anti-Ischemic Stroke Agents.
- 1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, Guizhou Medical University, Guian New Area, People's Republic of China.
Abstract
To identify novel therapeutic candidates for ischemic stroke, a series of hydrazine- and hydrazide-derived analogs based on 3-n-butylphthalide (NBP) were designed and synthesized in this study, and their anti-ischemic stroke activities were systematically assessed. Among all synthesized derivatives, the compound NBP-HY exerted potent antiplatelet aggregation and antioxidant activities in vitro. Consistent in vivo results revealed that NBP-HY significantly alleviated thrombus formation in both carrageenan-induced tail thrombosis and FeCl₃-induced carotid artery thrombosis models. In a rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model, NBP-HY markedly reduced cerebral infarct volume, improved cerebral blood perfusion, and protected hippocampal CA1 and cortical neurons, exhibiting superior therapeutic efficacy compared with the lead compound NBP. Further pharmacological experiments showed that NBP-HY exhibits moderate metabolic stability in liver microsomes, good blood-brain barrier permeability in the PAMPA-BBB model, and minimal impact on mice's physiological hemostatic function. Collectively, this work indicates that NBP‑HY has potential as a therapeutic candidate for ischemic stroke and warrants further in‑depth investigation.
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BibTeX
@article{li2026design,
title = {{Design, Synthesis of 3-n-Butylphthalide-Hydrazine/Hydrazide Derivatives as Potential Anti-Ischemic Stroke Agents.}},
author = {Yong Li and Manju Wang and Qing Zhang and Pengfei Zhou and Ya Yang and Lei Tang and Judi Fan and Lingling Fan},
journal = {Chemistry \& biodiversity},
year = {2026},
month = oct,
doi = {10.1002/cbdv.71866},
url = {https://europepmc.org/article/MED/42908397},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Design, Synthesis of 3-n-Butylphthalide-Hydrazine/Hydrazide Derivatives as Potential Anti-Ischemic Stroke Agents.
AU - Yong Li
AU - Manju Wang
AU - Qing Zhang
AU - Pengfei Zhou
AU - Ya Yang
AU - Lei Tang
AU - Judi Fan
AU - Lingling Fan
PY - 2026
DA - 2026/10/01
JO - Chemistry & biodiversity
DO - 10.1002/cbdv.71866
UR - https://europepmc.org/article/MED/42908397
AB - To identify novel therapeutic candidates for ischemic stroke, a series of hydrazine- and hydrazide-derived analogs based on 3-n-butylphthalide (NBP) were designed and synthesized in this study, and their anti-ischemic stroke activities were systematically assessed. Among all synthesized derivatives, the compound NBP-HY exerted potent antiplatelet aggregation and antioxidant activities in vitro. Consistent in vivo results revealed that NBP-HY significantly alleviated thrombus formation in both carrageenan-induced tail thrombosis and FeCl₃-induced carotid artery thrombosis models. In a rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model, NBP-HY markedly reduced cerebral infarct volume, improved cerebral blood perfusion, and protected hippocampal CA1 and cortical neurons, exhibiting superior therapeutic efficacy compared with the lead compound NBP. Further pharmacological experiments showed that NBP-HY exhibits moderate metabolic stability in liver microsomes, good blood-brain barrier permeability in the PAMPA-BBB model, and minimal impact on mice's physiological hemostatic function. Collectively, this work indicates that NBP‑HY has potential as a therapeutic candidate for ischemic stroke and warrants further in‑depth investigation.
SN - 1612-1872
SN - 1612-1880
ER -