dc.contributor.author | Engelbrecht, Idalet | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.contributor.author | Petzer, Anél | |
dc.date.accessioned | 2019-09-02T07:52:27Z | |
dc.date.available | 2019-09-02T07:52:27Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Engelbrecht, I. et al. 2019. Evaluation of selected natural compounds as dual inhibitors of catechol-o-methyltransferase and monoamine oxidase. Central nervous system agents in medicinal chemistry, 19(2):133-145. [https://doi.org/10.2174/1871524919666190619090852] | en_US |
dc.identifier.issn | 1871-5249 | |
dc.identifier.issn | 1875-6166 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/33266 | |
dc.identifier.uri | http://www.eurekaselect.com/172772/article | |
dc.identifier.uri | https://doi.org/10.2174/1871524919666190619090852 | |
dc.description.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 | en_US |
dc.language.iso | en | en_US |
dc.publisher | Bentham Science | en_US |
dc.subject | Catechol-O-methyltransferase | en_US |
dc.subject | Inhibition | en_US |
dc.subject | Monoamine oxidase | en_US |
dc.subject | Multi-target-directed | en_US |
dc.subject | Natural compounds | en_US |
dc.subject | Parkinson's disease | en_US |
dc.title | Evaluation of selected natural compounds as dual inhibitors of catechol-o-methyltransferase and monoamine oxidase | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 12264954 - Petzer, Anél | |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |
dc.contributor.researchID | 21639159 - Engelbrecht, Idalet | |