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Identification of 3-methyl-1-(3-methylpyridin-2-yl)-1H-pyrazol-5-ol as promising neuroprotective agent.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Dec 01; Vol. 114, pp. 129983. Date of Electronic Publication: 2024 Oct 10. - Publication Year :
- 2024
-
Abstract
- Pyrazolol derivatives are gaining significant attention for their diverse pharmacological effects, such as analgesic, anti-inflammatory, antioxidant, and anticancer activities. In this study, 20 pyrazolol derivatives were designed and synthesized to develop an anti-ischemic stroke formulation with free radical scavenging activity. Most of these synthesized compounds demonstrated antioxidant capabilities in DPPH, ABTS radical scavenging, and ORAC <subscript>FL</subscript> assays. The methyl-substituted compound Y12, in particular, showed exceptional antioxidant capacity. Additionally, these compounds showed excellent neurocytoprotective effects in the SH-SY5Y cell injury model subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Notably, Y12 exhibited significant metal chelating activity with Cu <superscript>2+</superscript> . In vivo studies confirmed that compound Y12 has neuroprotective effects and can significantly reduce the infarct area in a mouse model of focal cerebral ischemia induced by transient middle cerebral artery occlusion (tMCAO).<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Structure-Activity Relationship
Molecular Structure
Cell Line, Tumor
Antioxidants pharmacology
Antioxidants chemistry
Antioxidants chemical synthesis
Dose-Response Relationship, Drug
Infarction, Middle Cerebral Artery drug therapy
Neuroprotective Agents pharmacology
Neuroprotective Agents chemistry
Neuroprotective Agents chemical synthesis
Pyrazoles chemistry
Pyrazoles pharmacology
Pyrazoles chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 114
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 39395634
- Full Text :
- https://doi.org/10.1016/j.bmcl.2024.129983