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Volume 32, Issue 8
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Ischemic stroke, the most common type of cerebrovascular accident, is a major cause of severe disability among adults worldwide. Although there has been progress in interventions for ischemic stroke in the past decades, there is no effective treatment to prevent brain damage in acute ischemic stroke. Therefore, it is urgent to develop novel neuroprotective agents with a wide therapeutic time window to provide a better prognosis for ischemic stroke patients.

Objective

The current study aimed to synthesize novel derivatives with substituent cinnamide scaffolds, evaluate biological activity, and obtain neuroprotective agents.

Methods

The target compounds were synthesized using classical methods of medicinal chemistry. The neuroprotective effects against Glu-induced neurotoxicity injury were evaluated in PC12 cells by MTT assay. The cell apoptosis was analyzed by flow cytometer. The proteins were detected by western blotting. The neuroprotective activities were determined in two models of global and focal cerebral ischemia.

Results

Among the title compounds, , , and exhibited good neuroprotection and , which were selected and further studied to determine their mechanism of action. , , and protected PC12 cells against glutamate-induced apoptosis in a dose-dependent manner caspase-3 pathway. Moreover, the four compounds significantly reduced brain infarct area and exhibited excellent neuroprotective activities in the MCAO model.

Conclusion

Compounds , , and , as potent neuroprotective agents with anti-neurotoxicity activity and anticerebral infarction efficacy , might serve as a useful molecular tool for further physiology and pathophysiology function studies, leading to potential clinical therapeutic agents for ischemic injury.

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2025-04-10

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/content/journals/cmc/10.2174/0109298673302111240418060441
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Design, Synthesis, and Biological Evaluation of Novel Cinnamide Derivatives as Neuroprotective Agents for the Treatment of Cerebral Ischemia
Curr. Med. Chem. 32, 1635 (2025); https://doi.org/10.2174/0109298673302111240418060441
/content/journals/cmc/10.2174/0109298673302111240418060441
/content/journals/cmc/10.2174/0109298673302111240418060441
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  • Article Type:     Research Article
Keyword(s): anti-apoptosis; Caspase-3; cerebral ischemic stroke; Cinnamide; neuroprotective activity; PC12 cell

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