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Identification of 3-methyl-1-(3-methylpyridin-2-yl)-1H-pyrazol-5-ol as promising neuroprotective agent.

Authors :
Zhu P
Wu Y
Du Z
Li S
Li J
Lu X
Jiang X
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.)

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