Nature as a source and inspiration for human monoamine oxidase B (hMAO-B) inhibition: A review of the recent advances in chemical modification of natural compounds

ABSTRACT

Introduction

Over the past 5 years, we have witnessed intense research activity about the biological potential of natural products (NPs) as human monoamine oxidase B (hMAO-B) inhibitors. Despite the promising inhibitory activity, natural compounds often suffer from pharmacokinetic lissues, such as poor aqueous solubility, extensive metabolism, and low bioavailability.

Areas covered

This review provides an overview of the current landscape NPs as selective hMAO-B inhibitors and highlights their use as a starting scaffold to design (semi)synthetic derivatives to overcome the therapeutic (pharmacodynamic and pharmacokinetic) limitations of NPs and to obtain more robust structure–activity relationships (SARs) for each scaffold.

Expert opinion

All the natural scaffolds herein presented displayed a broad chemical diversity. The knowledge of their biological activity as inhibitors of hMAO-B enzyme allows the positive correlations associated with the consumption of specific food or the possible herb–drug interactions and suggests to the Medicinal Chemists how to address chemical functionalization to obtain more potent and selective compounds.

KEYWORDS:

• Natural compound
• MAO inhibitor
• chalcone
• flavonoid
• neurodegenerative diseases
• coumarin
• aurone
• phenolics

Article highlights

• NPs are a wide source of inspiration for new hMAO-B inhibitors

• Flavonoids and chalcones are the most investigated classes for hMAO-B inhibition

• Stilbenes and coumarins are the most chemically derivatized scaffolds to enhance inhibitory activity against hMAO-B

• Chemical functionalization can improve both pharmacodynamic and pharmacokinetic properties of NPs

• Some NP scaffolds can involve different biological properties beyond hMAO-B inhibition to counteract multifaceted diseases.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.