Discovery of reversible selective monoamine oxidase B inhibitors with anti-acetylcholinesterase activity derived from 4-oxo-N-4-diphenyl butanamides

Multitargeted drugs are essential for the treatment of various neurodegenerative disorders, because of their complex nature. This study aimed to develop novel small molecules as selective monoamine oxidase B (MAO-B) inhibitors with cholinesterase inhibition. With the help of fragment-based drug desi...

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Bibliographic Details
Published in:Future medicinal chemistry 2023-01, Vol.15 (2), p.189-210
Main Authors: Jana, Srabanti, Nasreen, Tania, Singh, Sushil K
Format: Article
Language:English
Subjects:
Alzheimer’s disease
cholinesterase
fragment-based drug design
Monoamine Oxidase - metabolism
monoamine oxidase B
Monoamine Oxidase Inhibitors - pharmacology
Structure-Activity Relationship
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Summary:Multitargeted drugs are essential for the treatment of various neurodegenerative disorders, because of their complex nature. This study aimed to develop novel small molecules as selective monoamine oxidase B (MAO-B) inhibitors with cholinesterase inhibition. With the help of fragment-based drug design, some 4-oxo-N-4-diphenyl butanamides were designed and synthesized as MAO-B inhibitors with anti-acetylcholinesterase (AChE) activity. Compound showed the best neuroprotection, with reversible selective MAO-B inhibition activity (IC = 11.54 ± 0.64 nM). Compounds , , , and (IC = 20.90 ± 0.50, 17.25 ± 0.90, 15.85 ± 0.16, 16.81 ± 0.85 and 25.19 ± 0.17 nM, respectively) also appeared as potent and selective MAO-B inhibitors with anti-AChE activity. The present study suggests potent, neuroprotective and nontoxic lead compounds as selective MAO-B inhibitors with anti-AChE activity.
ISSN:1756-8919
1756-8927
DOI:10.4155/fmc-2022-0169