Potent and Selective Monoamine Oxidase-B Inhibitory Activity: Fluoro- vs. Trifluoromethyl-4-hydroxylated Chalcone Derivatives

Mathew B., Mathew G. E. , Ucar G., BAYSAL İ. , Suresh J., Mathew S., ...Daha Fazla

CHEMISTRY & BIODIVERSITY, cilt.13, ss.1046-1052, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 13 Konu: 8
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1002/cbdv.201500367
  • Sayfa Sayıları: ss.1046-1052


For various neurodegenerative disorders like Alzheimer's and Parkinson's diseases, selective and reversible MAO-B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase-B (hMAO-B). In continuation of our earlier study and to extend the understanding of the structure-activity relationships, a series of five new chalcones were studied for their inhibition of hMAO. The results demonstrated that these compounds are reversible and selective hMAO-B inhibitors with a competitive mode of inhibition. The most active compound, (2E)-1-(4-hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one, exhibited a K-i value of 0.33 +/- 0.01 m toward hMAO-B with a selectivity index of 26.36. A molecular docking study revealed that the presence of a H-bond network in hydroxylated chalcone with the N(5) atom of FAD is crucial for MAO-B selectivity and potency.