Monoamine oxidase-B inhibitors as potential neurotherapeutic agents: An overview and update

Abstract

Monoamine oxidase (MAO) inhibitors have made significant contributions and remain an indispensable approach of molecular and mechanistic diversity for the discovery of antineurodegenerative drugs. However, their usage has been hampered by nonselective and/or irreversible action which resulted in drawbacks like liver toxicity, cheese effect, and so forth. Hence, the search for selective MAO inhibitors (MAOIs) has become a substantial focus in current drug discovery. This review summarizes our current understanding on MAO-A/MAO-B including their structure, catalytic mechanism, and biological functions with emphases on the role of MAO-B as a potential therapeutic target for the development of medications treating neurodegenerative disorders. It also highlights the recent developments in the discovery of potential MAO-B inhibitors (MAO-BIs) belonging to diverse chemical scaffolds, arising from intensive chemical-mechanistic and computational studies documented during past 3 years (2015-2018), with emphases on their potency and selectivity. Importantly, readers will gain knowledge of various newly established MAO-BI scaffolds and their development potentials. The comprehensive information provided herein will hopefully accelerate ideas for designing novel selective MAO-BIs with superior activity profiles and critical discussions will inflict more caution in the decision-making process in the MAOIs discovery.

Keywords: Alzheimer's disease; molecular modeling; monoamine oxidase-B; monoamine oxidase-B inhibitors; monoamine oxidases; neurodegenerative diseases.