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

Year 2022, Volume: 26 Issue: 5, 1461 - 1471, 28.06.2025

İrem Bozbey Gülce Taşkor Önel , Burçin Türkmenoğlu , Şule Gürsoy , Esra Dilek , Muhammed Ergün Azime Berna Özçelik , Mehtap Uysal

https://izlik.org/JA57LK27HS

Abstract

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 by 1H-NMR, 13CNMR,
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).

Keywords

Acetylcholinesterase , alzheimer’s disease , molecular docking , pyridazinone , triazole

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