Synthesis, anticholinesterase activity and molecular modeling study of novel carbamate-substituted thymol/carvacrol derivatives. Issue 4 (15th February 2017)

• Record Type: Journal Article
• Authors: Kurt, Belma Zengin; Gazioglu, Isil; Dag, Aydan; Salmas, Ramin Ekhteiari; Kayık, Gülru; Durdagi, Serdar; Sonmez, Fatih
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 4(2017)
• Page Start: 1352
• Page End: 1363
• Publication Date: 2017-02-15
• Subjects: Thymol -- Carvacrol -- Carbamate -- Alzheimer's disease -- Molecular docking -- Molecular dynamics (MD) simulations -- MM-PBSA -- Induced fit docking (IFD); Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.12.037
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: 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 IC50 values of 2.22 μM, and 5-isopropyl-2-methylphenyl (4-fluorophenyl)carbamate (30 ) exhibited the strongest inhibition against BuChE with IC50 value of 0.02 μM. Additionally, the result of H4IIE hepatoma cell toxicity assay for compounds18, 20, 29, 30 and35 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).