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., ...Daha Fazla

Journal of Research in Pharmacy, cilt.26, sa.5, ss.1461-1471, 2022 (Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 26 Sayı: 5
  • Basım Tarihi: 2022
  • Doi Numarası: 10.29228/jrp.239
  • Dergi Adı: Journal of Research in Pharmacy
  • Derginin Tarandığı İndeksler: Scopus, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.1461-1471
  • Anahtar Kelimeler: Acetylcholinesterase, alzheimer's disease, molecular docking, pyridazinone, triazole
  • Gazi Üniversitesi Adresli: Evet

Özet

© 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).