title: Synthesis and biological evaluation of some pyrazoline derivatives bearing a dithiocarbamate moiety as new cholinesterase inhibitors.
abstract: In the present study, new pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2-furyl)-5-aryl-2-pyrazolines with sodium salts of N,N-disubstituted dithiocarbamic acids. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The compounds were also investigated for their cytotoxic properties using the MTT assay. The most potent AChE inhibitor was found as compound 7 followed by compounds 27 and 17, when compared with eserine. Compounds effective on AChE carry the 2-dimethylaminoethyl moiety, which resembles the trimethylammonium group and the ethylene bridge of acetylcholine. Among all compounds, compound 7 bearing 2-dimethylaminoethyl and 3,4-methylenedioxyphenyl moieties was also found to be the most effective inhibitor of BuChE. The MTT assay indicated that the effective concentration of compound 7 was lower than its cytotoxic concentration.
authors: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, Eskişehir, Turkey. mdaltintop@anadolu.edu.tr
authors: Mehlika D
authors: MD
authors: Altintop
authors: Ahmet
authors: A
authors: Özdemir
authors: Zafer A
authors: ZA
authors: Kaplancikli
authors: Gülhan
authors: G
authors: Turan-Zitouni
authors: Halide E
authors: HE
authors: Temel
authors: Gülşen A
authors: GA
authors: Çiftçi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D011720:Pyrazoles / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D013859:Thiocarbamates / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D011720:Pyrazoles; D013778:Tetrazolium Salts; D013844:Thiazoles; D013859:Thiocarbamates; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C022616:thiazolyl blue