Methyl Yellow: A Potential Drug Scaffold for Parkinson's Disease. Issue 11 (8th July 2014)

• Record Type: Journal Article
• Authors: Geldenhuys, Werner J.; Kochi, Akiko; Lin, Li; Sutariya, Vijaykumar; Dluzen, Dean E.; Van der Schyf, Cornelis J.; Lim, Mi Hee
• Is Part Of: Chembiochem. Volume 15:Issue 11(2014)
• Page Start: 1591
• Page End: 1598
• Publication Date: 2014-07-08
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201300770
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>