title: Coumarin derivatives protect against ischemic brain injury in rats.
abstract: Neuroprotection strategies are of great importance in the treatment of ischemic brain injury. Screening of our in-stock coumarin derivatives identified compound 1 as exhibiting neuroprotective activity. Subsequently, a structural optimization was carried out, which led to the discovery of the potent compound 20. This compound significantly attenuated the damage in a cell line derived from a pheochromocytoma of the rat adrenal medulla induced by oxygen-glucose deprivation in vitro. Furthermore, compound 20 exhibited clear neuroprotection in middle cerebral artery occlusion rats by reducing infarct size and brain-water content, improving neurological function, and suppressing neuronal loss and neuropathological changes in the cortex and hippocampus. Pharmacokinetic evaluation indicated that compound 20 could penetrate the blood-brain barrier of rats.
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Rd., Xicheng Dist., Beijing 100050, PR China.
authors.forename: Mingna
authors.initials: M
authors.lastname: Sun
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Hu
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Song
authors.forename: Donghui
authors.initials: D
authors.lastname: Wu
authors.forename: Linglei
authors.initials: L
authors.lastname: Kong
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Sun
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Naihong
authors.initials: N
authors.lastname: Chen
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002545:Brain Ischemia / Q000517:prevention & control*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003374:Coumarins; D018696:Neuroprotective Agents; C030123:coumarin
keywords: Coumarin; Ischemic brain injury; Neuroprotective agents; Piperazine