Journal
PHARMACEUTICALS
Volume 14, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ph14090861
Keywords
Alzheimer's disease; ischemic stroke; multipotent drugs; neuroprotection; quinolylnitrones
Categories
Funding
- Instituto de Salud Carlos III [IFI18/00011]
- European Development Regional Fund (FEDER) [PI18/00255, RETICS RD16/0019/0006]
- Programa Miguel Servet [CPII19/00005, PI19/00082]
- MINECO (Government of Spain) [SAF-2015-65586-R]
- Spanish Ministry of Science, Innovation and Universities
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The article discusses the relationship between cerebrovascular diseases and dementia caused by Alzheimer's disease, highlighting the importance of developing new dual therapeutic agents. A new small quinolylnitrone, MC903, is proposed as a potential dual therapy for stroke and Alzheimer's disease.
Cerebrovascular diseases such as ischemic stroke are known to exacerbate dementia caused by neurodegenerative pathologies such as Alzheimer's disease (AD). Besides, the increasing number of patients surviving stroke makes it necessary to treat the co-occurrence of these two diseases with a single and combined therapy. For the development of new dual therapeutic agents, eight hybrid quinolylnitrones have been designed and synthesized by the juxtaposition of selected pharmacophores from our most advanced lead-compounds for ischemic stroke and AD treatment. Biological analyses looking for efficient neuroprotective effects in suitable phenotypic assays led us to identify MC903 as a new small quinolylnitrone for the potential dual therapy of stroke and AD, showing strong neuroprotection on (i) primary cortical neurons under oxygen-glucose deprivation/normoglycemic reoxygenation as an experimental ischemia model; (ii), neuronal line cells treated with rotenone/oligomycin A, okadaic acid or beta-amyloid peptide A beta(25-35), modeling toxic insults found among the effects of AD.
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