Inhibitory effects of novel 3(2H)pyridazinone-triazole derivatives against acetylcholinesterase enzyme


BOZBEY İ., TAŞKOR ÖNEL G., TÜRKMENOĞLU B., GÜRSOY Ş., DİLEK E., ERGÜN M., ...More

Journal of Research in Pharmacy, vol.26, no.5, pp.1461-1471, 2022 (Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 5
  • Publication Date: 2022
  • Doi Number: 10.29228/jrp.239
  • Journal Name: Journal of Research in Pharmacy
  • Journal Indexes: Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.1461-1471
  • Keywords: Acetylcholinesterase, alzheimer’s disease, molecular docking, pyridazinone, triazole
  • Gazi University Affiliated: Yes

Abstract

© 2022 Marmara University Press.Alzheimer's disease is a neurological disease characterized by the destruction of brain cells. In this disease, which causes a decrease in thought, memory and behavioral functions, the symptoms appear gradually with age. In this study, inhibition of acetylcholinesterase enzyme which is an important target in accordance with the cholinergic hypothesis, was studied. New 3(2H)pyridazinone-triazole derivatives were synthesized, confirmed by1H-NMR,13C-NMR, HRMS analysis and their IC50 and Ki values were studied. The inhibition constants (Ki) of the compounds against the AChE enzyme ranged from 2.35 ± 0.18 to 5.15 ± 0.46 µM. The compound with the best inhibitory properties was compound 6d with a Ki value of 2.35 ± 0.18 µM. In addition, to support the experimental data, molecular docking studies were carried out with 6b, 6d, 6e and 6f compounds with AChE crystal structure (PDB ID:4M0E).