SAR and molecular mechanism studies of monoamine oxidase inhibition by selected chalcone analogs

J Enzyme Inhib Med Chem. 2019 Dec;34(1):863-876. doi: 10.1080/14756366.2019.1593158.


The present study describes the synthesis of a series of 22 chalcone analogs. These compounds were evaluated as potential human MAO-A and MAO-B inhibitors. The compounds showed varied selectivity against the two isoforms. The IC50 values were found to be in the micromolar to submicromolar range. The Ki values of compound 16 were determined to be 0.047 and 0.020 μM for the inhibition of MAO-A and MAO-B, respectively. Dialysis of enzyme-inhibitor mixtures indicated a reversible competitive mode of inhibition. Most of the synthesized chalcone analogs showed a better selectivity toward MAO-B. However, introducing of 2,4,6-trimethoxy substituents on ring B shifted the selectivity toward MAO-A. In addition, we investigated the molecular mechanism of MAO-B inhibition by selected chalcone analogs. Our results revealed that these selected chalcone analogs increased dopamine levels in the rat hepatoma (H4IIE) cells and decreased the relative mRNA expression of the MAO-B enzyme.

Keywords: Monoamine oxidase; chalcone; dopamine; mRNA; reversibility.

MeSH terms

  • Chalcone / chemical synthesis
  • Chalcone / chemistry
  • Chalcone / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Structure-Activity Relationship


  • Monoamine Oxidase Inhibitors
  • Chalcone
  • Monoamine Oxidase

Grants and funding

This work was supported by internal grants from the Office of Academic Research, Qatar University, Doha, Qatar under Grants [# QUUG-CPH-15/16–7 and QUUG-CPH-2017–5]. The publication of this article was funded by the Qatar National Library, Doha, Qatar. The experiments dealing with the testing of the compounds in vitro were supported by the National Institutes on Alcohol Abuse and Alcoholism under Grant Number R01AA019458 (Y.S.). We are grateful to Professor Neal Castagnoli Jr. Professor Emeritus, Virginia Tech for providing the MMTP substrate. The biological section of this study was funded in part by the National Research Foundation of South Africa under Grant [number (UID) 85642, 96180].