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, 2020 (SCI-Expanded) identifier identifier

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.