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

• Published in: Future medicinal chemistry Vol. 15; no. 2; pp. 189 - 210
• Main Authors: Jana, Srabanti, Nasreen, Tania, Singh, Sushil K
• Format: Journal Article
• Language: English
• Published: England Newlands Press Ltd 01-01-2023
• Subjects: Alzheimer’s disease; cholinesterase; fragment-based drug design; Monoamine Oxidase - metabolism; monoamine oxidase B; Monoamine Oxidase Inhibitors - pharmacology; Structure-Activity Relationship; fragment-based drug design; Alzheimer’s disease; cholinesterase; monoamine oxidase B
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2022-0169

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.