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, cilt.196, sa.3, ss.283-293, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 196 Sayı: 3
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1080/10426507.2020.1830773
  • Dergi Adı: PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Sayfa Sayıları: ss.283-293
  • Anahtar Kelimeler: acetylcholinesterase inhibition, anticholinesterase activity, molecular modeling, piperazine, Thiazole
  • Eskişehir Osmangazi Üniversitesi Adresli: Hayır

Özet

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.