Synthesis, anticholinesterase activity and molecular modeling study of novel carbamate-substituted thymol/carvacrol derivatives

New thymol and carvacrol derivatives with the carbamate moiety were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. 5-isopropyl-2-methylphenyl(3-fluorophenyl)carbamate (29) was found to be the most potent AChE inhibitor with IC50values of 2.22 μM, and 5-isopropyl-2-methylphenyl (4-fluorophenyl)carbamate (30) exhibited the strongest inhibition against BuChE with IC50value of 0.02 μM. Additionally, the result of H4IIE hepatoma cell toxicity assay for compounds 18, 20, 29, 30 and 35 showed negligible cell death at 0.07–10 μM. Moreover in order to better understand the inhibitory profiles of these molecules, molecular modeling studies were applied. Binding poses of studied compounds at the binding pockets of AChE and BuChE targets were determined. Predicted binding energies of these compounds as well as structural and dynamical profiles of molecules at the target sites were estimated using induced fit docking (IFD) algorithms and post-processing molecular dynamics (MD) simulations methods (i.e., Molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) approaches).