Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies

A series of methoxylated chalcones with fluoro and trifluoromethyl derivatives were synthesized and investigated for their ability to inhibit human monoamine oxidase A and B. The chemical structures of the compounds have been characterized by means of their H-1 NMR, C-13 NMR, Mass spectroscopic datas and elemental analysis. The results demonstrate that these compounds are reversible and selective MAO-B inhibitors with a competitive mode of inhibition. The most potent compound (2E)-1-(4-methoxyphenyl)-3-[4-(trifluoromethyl)phenyl] prop-2-en-1-one showed the best activity and higher selectivity towards hMAO-B with K-i and SI values of 0.22 +/- 0.01 mu M and 0.05 comparable to that standard drug, Selegiline K-i and SI values were found as 0.33 +/- 0.03 mu M and 0.04, respectively. Molecular docking studies were carried out to further explain the in vitro results of the new compounds, and to identify the hypothetical binding mode for the compounds inside the inhibitor binding cavity of hMAO-B. (C) 2015 Elsevier Inc. All rights reserved.