Identification and optimization of nitrophenolic analogues as dopamine metabolic enzyme inhibitors for the treatment of Parkinson's disease.
Bioorg Chem
; 148: 107488, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38797066
ABSTRACT
Progressive loss of dopaminergic neurons leads to the depletion of the striatal neurotransmitter dopamine, which is the main cause of Parkinson's disease (PD) motor symptoms. Simultaneous inhibition of the two key dopamine metabolic enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B), could potentially be a breakthrough in achieving clinical efficacy. Representative compound C12 exhibits good COMT inhibitory activity (IC50 = 0.37 µM), metal chelation ability, and BBB permeability. Furthermore, results from in vivo biological activity evaluations indicate that C12 can improve dopamine levels and ameliorate MPTP-induced PD symptoms in mice. Preliminary in vivo and in vitro study results highlight the potential of compound C12 in PD treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Dopamina
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Monoaminoxidase
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Inibidores da Monoaminoxidase
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China