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

Sahin Z., Biltekin S. N., Buelbuel E. F., YURTTAŞ L., BERK B., DEMİRAYAK 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: acetylcholinesterase inhibition, anticholinesterase activity, molecular modeling, piperazine, Thiazole
  • Eskisehir Osmangazi University Affiliated: No

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 mu M in seven compounds (4a,4b,4h,4l,4m,4q,4r). Compounds4m,4b, and4lrepresented 1.15, 1.31, 1.34 mu M (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.