Synthesis and Biological Evaluation of Some Pyrazoline Derivatives Bearing a Dithiocarbamate Moiety as New Cholinesterase Inhibitors

ALTINTOP M. D., ÖZDEMİR A., KAPLANCIKLI Z. A., Turan-Zitouni G., TEMEL H. E., Ciftci G. A.

ARCHIV DER PHARMAZIE, vol.346, no.3, pp.189-199, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 346 Issue: 3
  • Publication Date: 2013
  • Doi Number: 10.1002/ardp.201200384
  • Journal Name: ARCHIV DER PHARMAZIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Page Numbers: pp.189-199
  • Keywords: Acetylcholinesterase, Anticholinesterase activity, Butyrylcholinesterase, Dithiocarbamate, Pyrazoline, ALZHEIMERS-DISEASE, ANTIBACTERIAL, CYTOTOXICITY
  • Anadolu University Affiliated: Yes

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.