Monoamine Oxidase Inhibitory Activity: Methyl- versus Chlorochalcone Derivatives

Mathew B., UÇAR G., Mathew G. E., Mathew S., Purapurath P. K., Moolayil F., ...More

CHEMMEDCHEM, vol.11, no.24, pp.2649-2655, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 11 Issue: 24
  • Publication Date: 2016
  • Doi Number: 10.1002/cmdc.201600497
  • Journal Name: CHEMMEDCHEM
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2649-2655
  • Hacettepe University Affiliated: Yes


Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase-B (MAO-B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO-B (hMAO-B) inhibitors, two series of twenty chalcones containing electron-donating and electron-withdrawing substituents were synthesized. All compounds were found to be competitive, selective, and reversible inhibitors of hMAO-B except (2E)-1-(4-methylphenyl)-3-(4-nitrophenyl) prop-2-en-1-one (P7) and (2E)-1-(4chlorophenyl)-3-(4-nitrophenyl) prop-2-en-1-one (P17), which were found to be selective inhibitors of hMAO-A. The most potent hMAO-B inhibitor, (2E)-1-(4-chlorophenyl)-3-(4-ethylphenyl) prop-2-en-1-one (P16), showed a Ki value of 0.11 : 0.01 mm. Molecular docking simulations were carried out to identify the hypothetical binding mode for the most potent compounds in the active sites of hMAO-A and B. The ability of the compounds to cross the blood-brain barrier was assessed by parallel artificial membrane permeability assay (PAMPA). Additionally, the most potent hMAO-B inhibitor P16 showed no toxicity in cultured hepatic cells at concentrations of 5 and 25 mu m.