Title: Dual monoamine oxidase B and acetylcholine esterase inhibitors for treating movement and cognition deficits in a C. elegans model of Parkinson's disease Boos J, Shubbar A, Geldenhuys WJ Ref: Med Chem Res, 30:1166, 2021 : PubMed
Parkinson's disease (PD) is an age-associated neurodegenerative movement disorder that leads to loss of dopaminergic neurons and motor deficits. Approaches to neuroprotection and symptom management in PD include use of monoamine oxidase B (MAO-B) inhibitors. Many patients with PD also exhibit memory loss in the later stages of disease progression, which is treated with acetylcholine esterase (AChE) inhibitors. We sought to identify a dual-mechanism compound that would inhibit both MAO-B and AChE enzymes. Our screen identified a promising compound (7) with balanced MAO-B (IC(50) of 16.83 microM) and AChE inhibition activity (AChE IC(50) of 22.04 microM). Application of this compound 7 increased short-term associative memory and significantly prevented 6-hydroxy-dopamine toxicity in dopaminergic neurons in the Caenorhabditis elegans nematode. These findings present a platform for future development of dual-mechanism drugs to treat neurodegenerative diseases such as PD.
        
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Boos J, Shubbar A, Geldenhuys WJ (2021) Dual monoamine oxidase B and acetylcholine esterase inhibitors for treating movement and cognition deficits in a C. elegans model of Parkinson's disease Med Chem Res30: 1166-1174
Boos J, Shubbar A, Geldenhuys WJ (2021) Med Chem Res30: 1166-1174