Monoamine oxidase inhibitory activity of methoxy-substituted chalcones


Mathew B., Mathew G. E. , UÇAR G. , Joy M., Nafna E. K. , Lohidakshan K. K. , ...More

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, vol.104, pp.1321-1329, 2017 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 104
  • Publication Date: 2017
  • Doi Number: 10.1016/j.ijbiomac.2017.05.162
  • Title of Journal : INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
  • Page Numbers: pp.1321-1329

Abstract

The MAO-B inhibitory activity of chalcone (1, 3-dipheny1-2-propen-1-one) based compounds arise from its structural similarity with 1, 4-diphenyl-2-butene, a known MAO-B inhibitor. Based on our previous report, the methoxy-substituted with fluorine containing chalcones are promising reversible MAO-B inhibitors, while in the present study, a series of methoxylated chalcones (C1-C9) bearing substitution on the para position of ring B was synthesized and evaluated for their human monoamine oxidase inhibitory activity. With the exception of (2E)-1-(4-methoxyphenyl)-3-(4-nitrophenyl) prop 2-en-1-one (C7), which is a nonselective inhibitor, the chalcones exhibited competitive, selective, and reversible inhibition of hMAO-B. The most potent compound, (2E)-3-[4-(dimethylamino) phenyl]1-(4-methoxyphenyl) prop-2-en-1-one (C5), showed the best inhibitory activity towards hMAO-B (IC50 = 0.29 +/- 0.011 mu M; K-i; = 0.14 +/- 0.001 mu M). The reversibility of MAO-B inhibition by compound C5 was demonstrated by the recovery of enzyme activity after dialysis of mixtures containing enzyme and inhibitor. The reversiblity of C5 was 25.38 +/- 1.40 and 92.00 +/- 3.87% before and after dialysis, respectively. PAMPA was carried out to evaluate the blood-brain barrier effects of the designated compounds. Moreover, the most potent MAO-B inhibitor, C5, was found to be nontoxic towards cultured hepatic cells at 5 and 25 mu M, with 97 and 90% viability. Molecular docking study was performed against hMAO-B to observe the binding site interactions of the lead compound. (C) 2017 Elsevier B.V. All rights reserved.