Open AccessDual monoamine oxidase B and acetylcholine esterase inhibitors for treating movement and cognition deficits in a C. elegans model of Parkinson’s disease
Author(s) -
Jacob R Boos,
Ahmed Shubbar,
Werner J. Geldenhuys
Publication year - 2021
Publication title -
medicinal chemistry research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.352
H-Index - 45
eISSN - 1554-8120
pISSN - 1054-2523
DOI - 10.1007/s00044-021-02720-x
Subject(s) - dopaminergic , monoamine oxidase b , chemistry , dopamine , acetylcholine , monoamine oxidase , pharmacology , neuroprotection , caenorhabditis elegans , monoamine neurotransmitter , neuroscience , psychology , biochemistry , enzyme , medicine , serotonin , receptor , gene
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 μM) and AChE inhibition activity (AChE IC 50 of 22.04 μM). 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.