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.

Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives

“…The first method (method A) was a two-step method which involved the reaction of the appropriate primary alcohol or secondary amine with carbon disulfide in the presence of potassium hydroxide to give O-alkyl dithiocarbonates (3a-d) and N,N-disubstituted dithiocarbamates (5a-h) following the previously reported procedures 1,2,7,[40][41][42] . The latter compounds 3 and 5 were reacted with equimolar amount of the chloromethyl derivative 2 at room temperature to afford carbodithioate derivatives (4a-d) and carbamodithioates (6a-g) and (7) in poor to good yields (39-89%).…”

“…Potassium salts of N,N-disubstitued dithiocarbamic acids (5a-h) 1,2,7,40,42 Potassium hydroxide (0.28 g, 5 mmol) was dissolved in ethanol (20 mL) then the appropriate secondary amine (5 mmol) was added and the mixture was cooled in an ice bath. Carbon disulphide (4 mL, 50 mmol) was added to the mixture drop-wise with stirring.…”

Water‐Involved C−S Bond Formation for the Synthesis of β‐Keto Dithiocarbamates from Thiuram Disulfides

“…Dithiocarbamates are a popular class of sulfur-containing compounds in organic chemistry owing to their versatile biological and pharmaceutical activities, [1] as well as their important applications in organic synthesis. Many compounds containing this skeleton have been found to be biologically active, they could be served as useful drugs or inhibitors, such as anti-cancer drugs (a), [2] cholinesterase inhibitors (b), [3] microbicidal spermicids (c), [4] crue accelerators (d), [5] epidermal growth factor receptors (EGFR) (e), [6] non-surfactant dual action vaginal spermicides (f), [7] monoacylglycerol lipase inhibitors, [8] leukemic cell inhibitors, [9] anti-hypertensive drugs, [10] rubber additives, additives of polluted water. [11] Furthermore, dithiocarbamates and its derivatives are also important general synthetic intermediates in organic synthesis (Figure 1).…”

Yeni piperazin bileşiklerinin sentezi ve antikolinesteraz etkilerinin araştırılması

“…For instance, it was found out that the existence of benzyl piperazine moiety in the compounds provide inhibitor effect thanks to interaction with AChE's catalytic site 22 . In another assay, it was indicated that piperazine derivatives were more effective than other heterocyclic compounds on AChE activity 23 .…”