Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease.

Title

Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease.

Creator

Geldenhuys Werner J; Kochi Akiko; Lin Li; Sutariya Vijaykumar; Dluzen Dean E; Van der Schyf Cornelis J; Lim Mi Hee

Publisher

Chembiochem : a European journal of chemical biology

Date

2014
2014-07

Description

Parkinson's disease (PD) is an age-related neurodegenerative disease affecting movement. To date, there are no currently available therapeutic agents which can prevent or slow disease progression. Here, we evaluated an azobenzene derivative, methyl yellow (MY), as a potential drug scaffold for PD; its inhibitory activity toward monoamine oxidase B (MAO-B) as well as drug-like properties were investigated. The inhibitory effect of MY on MAO activity was determined by a MAO enzyme inhibition assay. In addition, the in vitro properties of MY as a drug candidate (e.g., blood-brain barrier (BBB) permeability, serum albumin binding, drug efflux through P-glycoprotein (P-gp), drug metabolism by P450, and mitochondrial toxicity) were examined. In vivo effectiveness of MY was also evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian mouse model. MY selectively inhibited MAO-B in a dose-dependent and reversible manner. MY was BBB-permeable, bound relatively weakly to serum albumin, was an unlikely substrate for both systems of P-gp and P450, and did not cause mitochondrial toxicity. Results from the MPTP Parkinsonian mouse model indicated that, upon treatment with MY, neurotoxicity induced by MPTP was mitigated. Investigations of MY demonstrate its inhibitory activity toward MAO-B, compliant properties for drug consideration, and its neuroprotective capability in the MPTP Parkinsonian mouse model. These data provide insights into potential use, optimization, and new design of azobenzene derivatives for PD treatment.

Subject

*MAO-B inhibitor; *methyl yellow; *MPTP mouse model; *Parkinson's disease; *TMRM

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1591–1598

Issue

11

Volume

15

Citation

Geldenhuys Werner J; Kochi Akiko; Lin Li; Sutariya Vijaykumar; Dluzen Dean E; Van der Schyf Cornelis J; Lim Mi Hee, “Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease.,” NEOMED Bibliography Database, accessed March 8, 2021, https://neomed.omeka.net/items/show/2986.

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