Design and synthesis of new donepezil analogs derived from arylpiperazine scaffold as acetylcholinesterase inhibitors

Sahin Z., Biltekin S. N., Bülbül E. F., YURTTAŞ L., Berk B., Demirayak Ş.

Phosphorus, Sulfur and Silicon and the Related Elements, vol.196, no.3, pp.283-293, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 196 Issue: 3
  • Publication Date: 2020
  • Doi Number: 10.1080/10426507.2020.1830773
  • Journal Name: Phosphorus, Sulfur and Silicon and the Related Elements
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Page Numbers: pp.283-293
  • Keywords: Thiazole, piperazine, anticholinesterase activity, acetylcholinesterase inhibition, molecular modeling
  • Istanbul Medipol University Affiliated: Yes

Abstract

Newly synthesized 4-substituted phenyl-2-(4-substituted phenylpiperazine-1-yl)thiazole derivatives (4a–v) were evaluated in terms of their acetylcholinesterase (AChE) inhibition activities. Twenty-two compounds were tested against AChE at six different concentrations that varied between 10−4 and 10−9 M. The concentrations that inhibited AChE were calculated between 1.15 and 3.45 µM in seven compounds (4a, 4b, 4h, 4l, 4m, 4q, 4r). Compounds 4m, 4b, and 4l represented 1.15, 1.31, 1.34 µM (IC50) inhibitions, respectively. Although the inhibition values are lower than that of donepezil, they are considerable. Modeling studies of these analogs revealed similar positioning with donepezil, in which Ar–Ar interactions with Tyr337 and Trp 286 exist.