Novel thiazole-piperazine derivatives as potential cholinesterase inhibitors

DEMİRAYAK Ş., Sahin Z., Ertas M., Bulbul E. F., Bender C., Biltekin S. N., ...More

JOURNAL OF HETEROCYCLIC CHEMISTRY, vol.56, no.12, pp.3370-3386, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 56 Issue: 12
  • Publication Date: 2019
  • Doi Number: 10.1002/jhet.3734
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Page Numbers: pp.3370-3386
  • Anadolu University Affiliated: Yes


Dementia is a cognitive disorder mostly associated with Alzheimer's disease (AD) in addition to being seen in many other diseases of the central nervous system (CNS). The limited number of drugs is not sufficient to provide adequate improvement to increase the quality of life of patients suffering from this symptom; therefore, all treatment options should be evaluated in detail. In this study, new molecules, [2-(4-(2/3/4-substituted phenyl)piperazin-1-yl)-4-phenylthiazol-5-yl][3/4-substituted phenyl]methanone derivatives (1-44), were obtained and analyzed in terms of their anticholinesterase activities. Kinetic mode and molecular interactions were also evaluated. An enzyme inhibition study was undertaken on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the Ellman method. Maestro program was used in molecular modeling studies. Forty-four compounds were evaluated on AChE and BChE enzymes at 10(-3) and 10(-4) concentrations. The inhibition concentrations were calculated as 0.268 mu M to 2.104 mu M for six compounds (4, 5, 16, 27, 37, and 38) on AChE. Compound 5 including the 4-methoxy substituent (IC50: 0.268 mu M) and compound 38 containing the 4-methoxy and 3-methyl substituents (IC50: 0.286 mu M) showed the highest AChE inhibitory activity. They were further examined in terms of hydrogen bonding with Arg296 and Ar-Ar interaction with Trp286. The activity of compound 5 was also assessed in mixed-type kinetic mode.