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

ALTINTOP M. D., ALP A. S., ÖZKAY Y., KAPLANCIKLI Z. A.

ARCHIV DER PHARMAZIE, cilt.346, sa.8, ss.571-576, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 346 Sayı: 8
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1002/ardp.201300045
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Sayfa Sayıları: ss.571-576
  • Anahtar Kelimeler: Acetylcholinesterase, Anticholinesterase, Butyrylcholinesterase, Dithiocarbamate, ALZHEIMERS-DISEASE, ACETYLCHOLINESTERASE, DERIVATIVES, DOCKING, DESIGN, AGENTS
  • Anadolu Üniversitesi Adresli: Evet

Özet

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. H-1 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. 2g (IC50=0.53 +/- 0.001 mu M) followed by compounds 2f (IC50=0.74 +/- 0.001 mu M) and 2j (IC50=0.89 +/- 0.002 mu M) when compared with donepezil (IC50=0.048 +/- 0.001 mu M). Compounds 2f and 2g were more effective than donepezil (IC50=7.88 +/- 0.52 mu M) 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 mu M, respectively.