Novel approaches to the discovery of selective human monoamine oxidase-B inhibitors: is there room for improvement?

Abstract

Introduction: Selective monoamine oxidase-B (MAO-B) inhibitors are currently used as coadjuvants for the treatment of early motor symptoms in Parkinson's disease. They can, based on their chemical structure and mechanism of inhibition, be categorized into reversible and irreversible agents. Areas covered: This review provides a comprehensive update on the development state of selective MAO-B inhibitors describing the results, structures, structure-activity relationships (SARs) and Medicinal chemistry strategies as well as the related shortcomings over the past five years. Expert opinion: Researchers have explored and implemented new and old chemical scaffolds achieving high inhibitory potencies and isoform selectivity. Most of them were characterized and proposed as multitarget agents able to act at different levels (including AChE inhibition, H3R or A_2AR antagonism, antioxidant and chelating properties, Aβ_1-42 aggregation reduction) in the network of aetiologies of neurodegenerative disorders. These results can also be used to avoid 'cheese-reaction' effects and the occurrence of serotonergic syndrome in patients.

Keywords: Benzyloxy; coumarins; flavonoids; monoamine oxidase B inhibitors; oxazolidinones; pyrazolines; thiosemicarbazones.