6-Methyluracil derivatives as peripheral site ligand-hydroxamic acid conjugates: Reactivation for paraoxon-inhibited acetylcholinesterase.
Eur J Med Chem
; 185: 111787, 2020 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-31675511
ABSTRACT
New uncharged conjugates of 6-methyluracil derivatives with imidazole-2-aldoxime and 1,2,4-triazole-3-hydroxamic acid units were synthesized and studied as reactivators of organophosphate-inhibited cholinesterase. Using paraoxon (POX) as a model organophosphate, it was shown that 6-methyluracil derivatives linked with hydroxamic acid are able to reactivate POX-inhibited human acetylcholinesterase (AChE) in vitro. The reactivating efficacy of one compound (5b) is lower than that of pyridinium-2-aldoxime (2-PAM). Meanwhile, unlike 2-PAM, in vivo study showed that the lead compound 5b is able (1) to reactivate POX-inhibited AChE in the brain; (2) to decrease death of neurons and, (3) to prevent memory impairment in rat model of POX-induced neurodegeneration.
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Base de dados:
MEDLINE
Assunto principal:
Paraoxon
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Acetilcolinesterase
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Uracila
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Inibidores da Colinesterase
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Ácidos Hidroxâmicos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article