title: Synthesis and biological evaluation of a series of dithiocarbamates as new cholinesterase inhibitors.
abstract: In the present paper, a novel series of dithiocarbamates was synthesized via the treatment of 4-(trifluoromethyl)benzyl chloride with appropriate sodium salts of N,N-disubstituted dithiocarbamic acids. The chemical structures of the compounds were elucidated by (1) H NMR, mass spectral data, and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The most potent AChE inhibitor was found as compound 2g (IC50  = 0.53 ± 0.001 µM) followed by compounds 2f (IC50  = 0.74 ± 0.001 µM) and 2j (IC50  = 0.89 ± 0.002 µM) when compared with donepezil (IC50  = 0.048 ± 0.001 µM). Compounds 2f and 2g were more effective than donepezil (IC50  = 7.88 ± 0.52 µM) on BuChE inhibition. Compounds 2f and 2g exhibited the inhibitory effect on BuChE with IC50 values of 1.39 ± 0.041 and 3.64 ± 0.072 µM, respectively.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, Eskişehir, Turkey. mdaltintop@anadolu.edu.tr
authors.forename: Mehlika D
authors.initials: MD
authors.lastname: Altıntop
authors.forename: A Selen
authors.initials: AS
authors.lastname: Gurkan-Alp
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ozkay
authors.forename: Zafer A
authors.initials: ZA
authors.lastname: Kaplancıklı
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011487:Protein Conformation; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D013859:Thiocarbamates; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Anticholinesterase; Butyrylcholinesterase; Dithiocarbamate