Evaluation of Selected Natural Compounds as Dual Inhibitors of Catechol-O-Methyltransferase and Monoamine Oxidase.
Cent Nerv Syst Agents Med Chem
; 19(2): 133-145, 2019.
Article
em En
| MEDLINE
| ID: mdl-31258092
ABSTRACT
BACKGROUND:
The most effective symptomatic treatment of Parkinson's disease remains the metabolic precursor of dopamine, L-dopa. To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine.OBJECTIVE:
This study attempted to discover compounds that exhibit dual inhibition of COMT and MAO-B among a library of 40 structurally diverse natural compounds. Such dual acting inhibitors may be effective as adjuncts to L-dopa and offer enhanced value in the management of Parkinson's disease.METHODS:
Selected natural compounds were evaluated as in vitro inhibitors of rat liver COMT and recombinant human MAO. Reversibility of MAO inhibition was investigated by dialysis.RESULTS:
Among the natural compounds morin (IC50 = 1.32 µM), chlorogenic acid (IC50 = 6.17 µM), (+)-catechin (IC50 = 0.86 µM), alizarin (IC50 = 0.88 µM), fisetin (IC50 = 5.78 µM) and rutin (IC50 = 25.3 µM) exhibited COMT inhibition. Among these active COMT inhibitors only morin (IC50 = 16.2 µM), alizarin (IC50 = 8.16 µM) and fisetin (IC50 = 7.33 µM) were noteworthy MAO inhibitors, with specificity for MAO-A.CONCLUSION:
None of the natural products investigated here are dual COMT/MAO-B inhibitors. However, good potency COMT inhibitors have been identified, which may serve as leads for future development of COMT inhibitors.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
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Catecol O-Metiltransferase
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Inibidores de Catecol O-Metiltransferase
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Monoaminoxidase
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Inibidores da Monoaminoxidase
Idioma:
En
Revista:
Cent Nerv Syst Agents Med Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
África do Sul