Synthesis and Biological Evaluation of a Series of Dithiocarbamates as New Cholinesterase Inhibitors

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 (IC 50  = 0.53 ± 0.001 µM) followed by compounds 2f (IC 50  = 0.74 ± 0.001 µM) and 2j (IC 50  = 0.89 ± 0.002 µM) when compared with donepezil (IC 50  = 0.048 ± 0.001 µM). Compounds 2f and 2g were more effective than donepezil (IC 50  = 7.88 ± 0.52 µM) on BuChE inhibition. Compounds 2f and 2g exhibited the inhibitory effect on BuChE with IC 50 values of 1.39 ± 0.041 and 3.64 ± 0.072 µM, respectively.