Unexpected AChE inhibitory activity of (2E)α,β-unsaturated fatty acids.

Basic Information

ID: ALA4261594

Journal: Bioorg Med Chem Lett

Title: Unexpected AChE inhibitory activity of (2E)α,β-unsaturated fatty acids.

Authors: Loesche A, Wiemann J, Al Halabi Z, Karasch J, Sippl W, Csuk R.

Abstract: A small library of (E) α,β-unsaturated fatty acids was prepared, and 20 different saturated and mono-unsaturated fatty acids differing in chain length were subjected to Ellman's assays to determine their ability to act as inhibitors for AChE or BChE. While the compounds were only very weak inhibitors of BChE, seven molecules were inhibitors of AChE holding IC50 = 4.3-12.8 M with three of them as significant inhibitors of this enzyme. The results have shown trans 2-mono-unsaturated fatty acids are better inhibitors for AChE than their saturated analogs. Furthermore, the screening results indicate that the chain length is crucial for obtaining an inhibitory efficacy. The best results were obtained for (2E) eicosenoic acid (14) showing inhibition constants Ki = 1.51 ± 0.09 M and Ki' = 7.15 ± 0.55 M. All tested compounds were mixed-type inhibitors with a dominating competitive part. Molecular modelling calculations indicate a different binding mode of active/inactive compounds for the enzymes AChE and BChE.

CiteXplore: 30220607

DOI: 10.1016/j.bmcl.2018.09.013

Patent ID: ┄