Novel (p-tolyl)-3(2H)-pyridazinone derivatives containing substituted-1,2,3-triazole moiety as new anti-Alzheimer agents: Synthesis, in vitro and in silico assays

Year 2022, Volume: 47 Issue: 3, 355 - 368, 19.10.2022

İrem Bozbey , Gülce Taşkor Önel , Burçin Türkmenoğlu , Şule Gürsoy , Esra Dilek

https://doi.org/10.55262/fabadeczacilik.1128446

Cited By: 1

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disease that is the most common cause of dementia. The risk of developing the disease increases with age. When the histopathology of the disease is examined, senile amyloid plaques, neurofibrillary tangle formation, synapse-neuron loss and marked atrophy in the brain are detected. The decrease in the level of choline acetyltransferase, which is responsible for the synthesis of acetylcholine in Alzheimer's disease, is 58-90%. There is a great need for new drugs that target the basis of the cause of the disease, as existing drugs cannot stop the progression of the disease. In this study, triazole-pyridazinone derivative compounds showing acetylcholinesterase inhibition were synthesized and their inhibitions were investigated. Compound 6e exhibited the strongest inhibitory effect with a Ki value of 0.049 ± 0.014 µM (Tacrine Ki= 0.226 ± 0.025 µM). In addition, in silico studies were applied for all compounds.

Keywords

3(2H)-pyridazinone, Acetylcholinesterase, molecular docking

Thanks

The authors would like to thank Erzincan Binali Yıldırım University, Basic Sciences Application and Research Center (EBYU-EUTAM) for the Schrödinger Maestro 2021-2 program.

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