Title:Comparison of Novel Tacrine and 7-MEOTA Derivatives with Aromatic and Alicyclic Residues: Synthesis, Biological Evaluation and Docking Studies
VOLUME: 10 ISSUE: 4
Author(s):Jan Korabecny, Ladislav Janovec, Kamil Musilek, Filip Zemek, Anna Horova, Eugenie Nepovimova, Rafael Dolezal, Veronika Opletalova, Jana Hroudova, Zdenek Fisar, Young-Sik Jung and Kamil Kuca
Affiliation:Centre of Advanced Studies, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Keywords:7-methoxytacrine, acetylcholinesterase, Alzheimer`s disease, butyrylcholinesterase, inhibition selectivity, molecular
modelling.
Abstract:Cholinesterase inhibitors play an essential role in the treatment of Alzheimer’s disease. Since their first introduction
over a decade ago, they are an indispensable part of Alzheimer’s disease therapy and remain at the forefront of
scientific interest worldwide. In this manuscript new analogs of THA and 7-MEOTA were designed, synthesized, and
evaluated for their inhibitory activity against both acetylcholinesterase and butyrylcholinesterase. Cholinergic properties
were investigated and quantified with respect to their side chain residues (aromatic or alicyclic). All synthesized compounds
proved to have potent inhibitory activity at micromolar range. Moreover, compound 4 demonstrated promising efficacy
and appears to be an ideal candidate for further testing.
