Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase

Ceyhun I., Karaca Ş., OSMANİYE D., SAĞLIK B. N., LEVENT S., ÖZKAY Y., ...More

ARCHIV DER PHARMAZIE, vol.355, no.3, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 355 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1002/ardp.202100372
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database, Index Chemicus (IC)
  • Keywords: Alzheimer's disease, benzofuran, beta-amyloid, chalcone, BIOLOGICAL EVALUATION, MONOAMINE-OXIDASE, ALZHEIMERS-DISEASE, IN-SILICO, ANALOGS
  • Anadolu University Affiliated: Yes


According to the cholinergic hypothesis, an increase in the acetylcholine level in Alzheimer's disease patients relatively slows down the symptoms of the disease. The most commonly used drug, donepezil, is a cholinesterase inhibitor. In this study, 12 new chalcones (2a-l) were designed and synthesized. In biological activity studies, the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 2d, 2f, 2j, and 2l displayed significant activity against AChE. The compounds 2d, 2f, 2j, and 2l displayed IC50 values of 0.042, 0.024, 0.053, and 0.033 mu M against AChE, respectively. The reference drug donepezil (IC50 = 0.021 mu M) also displayed significant inhibition of AChE. The inhibitory activities of these compounds for beta-amyloid plaque aggregation were investigated. The enzyme kinetic study was performed to observe the effect of the most active compound 2f on the substrate-enzyme relationship, and a mixed-type inhibition of AchE was determined. Further, docking simulation also revealed that these compounds (2d, 2f, 2j, and 2l) interacted with the enzyme active site in a similar manner to donepezil. The most active derivative, compound 2f, interacted with the amino acids Trp286, Phe295, Tyr341, Trp86, and Glu202.