{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:42:10Z","timestamp":1792654930900,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260686"],"award-info":[{"award-number":["82260686"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n To identify novel therapeutic candidates for ischemic stroke, a series of hydrazine\u2010 and hydrazide\u2010derived analogs based on 3\u2010\n n<\/jats:italic>\n \u2010butylphthalide (NBP) were designed and synthesized in this study, and their anti\u2010ischemic stroke activities were systematically assessed. Among all synthesized derivatives, the compound\n NBP\u2010HY<\/jats:bold>\n exerted potent antiplatelet aggregation and antioxidant activities in vitro. Consistent in vivo results revealed that\n NBP\u2010HY<\/jats:bold>\n significantly alleviated thrombus formation in both carrageenan\u2010induced tail thrombosis and FeCl\n 3<\/jats:sub>\n \u2010induced carotid artery thrombosis models. In a rat middle cerebral artery occlusion\/reperfusion (MCAO\/R) injury model,\n NBP\u2010HY<\/jats:bold>\n 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\u2010HY exhibits moderate metabolic stability in liver microsomes, good blood\u2013brain barrier permeability in the PAMPA\u2010BBB model, and minimal impact on mice's physiological hemostatic function. Collectively, this work indicates that\n NBP\u2011HY<\/jats:bold>\n has potential as a therapeutic candidate for ischemic stroke and warrants further in\u2011depth investigation.\n <\/jats:p>","DOI":"10.1002\/cbdv.71866","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:32:04Z","timestamp":1792654324000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis of 3\u2010\n n<\/i>\n \u2010Butylphthalide\u2010Hydrazine\/Hydrazide Derivatives as Potential Anti\u2010Ischemic Stroke Agents"],"prefix":"10.1002","volume":"23","author":[{"given":"Yong","family":"Li","sequence":"first","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manju","family":"Wang","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhou","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Yang","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tang","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judi","family":"Fan","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5607-3813","authenticated-orcid":false,"given":"Lingling","family":"Fan","sequence":"additional","affiliation":[{"name":"State 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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1177\/17474930241308142","article-title":"World Stroke Organization: Global Stroke Fact Sheet 2025","volume":"20","author":"Feigin V. L.","year":"2025","journal-title":"International Journal of Stroke"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41401-023-01061-2","article-title":"Angiogenesis After Ischemic Stroke","volume":"44","author":"Fang J.","year":"2023","journal-title":"Acta Pharmacologica Sinica"},{"key":"e_1_2_9_4_1","first-page":"1","article-title":"Current Advances in Ischemic Stroke Research and Therapies","volume":"1866","author":"Barthels D.","year":"2020","journal-title":"BBA Molecular Basis of Disease"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2025.1581320","article-title":"Edaravone Dexborneol Protected Neurological Function by Targeting NRF2\/ARE and NF\u2010\u03baB\/AIM2 Pathways in Cerebral Ischemia\/Reperfusion Injury","volume":"16","author":"Zhang H.","year":"2025","journal-title":"Frontiers in pharmacology"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"12485","DOI":"10.1021\/acs.jmedchem.0c00887","article-title":"From Seeds of Apium graveolens Linn. to a Cerebral Ischemia Medicine: The Long Journey of 3\u2010n\u2010Butylphthalide","volume":"63","author":"Marco\u2010Contelles J.","year":"2020","journal-title":"Journal of Medicinal Chemistry"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.987293","article-title":"dl\u20103\u2010n\u2010Butylphthalide (NBP) Alleviates Poststroke Cognitive Impairment (PSCI) by Suppressing Neuroinflammation and Oxidative Stress","volume":"13","author":"Zhang H.","year":"2023","journal-title":"Frontiers in Pharmacology"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2025.115343","article-title":"3\u2010n\u2010Butylphthalide Improves Cerebral Ischemia\/Reperfusion Injury by Regulating Neuronal Mitochondrial Biogenesis via AMPK\/PGC\u20101\u03b1 Signaling Pathway","volume":"164","author":"Li J.","year":"2025","journal-title":"International Immunopharmacology"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jchromb.2021.122915","article-title":"Absorption, Distribution, Metabolism, and Excretion of [14C]NBP (3\u2010n\u2010Butylphthalide) in Rats","volume":"1181","author":"Tian J. 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W.","year":"2020","journal-title":"Pakistan Journal of Medical Sciences"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.175801","article-title":"A Comparative Study of the Neuroprotective Effects of dl\u20103\u2010n\u2010Butylphthalide and Edaravone Dexborneol on Cerebral Ischemic Stroke Rats","volume":"951","author":"Zhang H.","year":"2023","journal-title":"European Journal of Pharmacology"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2024.1415977","article-title":"Effects of Butylphthalide Sodium Chloride Injection Combined With Edaravone Dexborneol on Neurological Function and Serum Inflammatory Factor Levels in Sufferers Having Acute Progressive Cerebral Infarction","volume":"15","author":"Li Y. Q.","year":"2024","journal-title":"Frontiers in Neurology"},{"key":"e_1_2_9_13_1","first-page":"1820","article-title":"Research Advance of Acylhydrazine Derivatives With Biological Activities","volume":"30","author":"Ke S. 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