| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1392638 | European Journal of Medicinal Chemistry | 2013 | 15 Pages |
•36 new 3-piperazinyl coumarins have been designed and synthesized.•All of the compounds have been evaluated for neuroprotective activity in vitro.•Compound 20 showed significant neuroprotection in vitro and in MCAO rats.•Mechanistic studies indicated that 20 exhibited antiapoptosis of neurons.•Pharmacokinetic evaluation indicated that 20 could cross the BBB of rats.
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.
Graphical abstractA series of novel coumarin derivatives were designed and synthesized. The most effective compound 20 showed significant neuroprotection in MCAO rats.Figure optionsDownload full-size imageDownload as PowerPoint slide
