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Journals / Fabad Eczacılık Bilimler Dergisi / 2022 / Cilt: 47 Sayı: 3

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

İrem Bozbey(Erzincan Binali Yıldırım Üniversitesi Eczacılık Fakültesi Farmasötik Kimya AbD)0000-0002-9290-938X
Gülce Taşkor Önel(Erzincan Binali Yıldırım Üniversitesi Eczacılık Fakültesi Analitik Kimya AbD)0000-0002-9375-2329
Burçin Türkmenoğlu(Erzincan Binali Yıldırım Üniversitesi Eczacılık Fakültesi Analitik Kimya AbD)0000-0002-5770-0847
Şule Gürsoy(Erzincan Binali Yıldırım Üniversitesi Eczacılık Fakültesi Biyokimya AbD)0000-0001-5236-5974
Esra Dilek(Erzincan Binali Yıldırım Üniversitesi Eczacılık Fakültesi Biyokimya AbD)0000-0002-3629-5168
Pages
355–368
Publication Date
2022-10-19
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In addition, in silico studies were applied for all compounds.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Alzheimer's disease (AD) is a chronic neurodegenerative disease that is the most common cause of dementia.
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Key Findings & Data:The risk of developing the disease increases with age.
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Conclusion & Impact:In addition, in silico studies were applied for all compounds.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:3(2H)-piridazinon · Asetilkolinesteraz · moleküler docking

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.

Özet

Alzheimer hastalığı (AH), demansın en yaygın nedeni olan kronik nörodejeneratif bir hastalıktır. Hastalığa yakalanma riski yaşla birlikte artar. Hastalığın histopatolojisi incelendiğinde senil amiloid plakları, nörofibriler yumak oluşumu, sinaps-nöron kaybı ve beyinde belirgin atrofi saptanır. Alzheimer hastalığında asetilkolin sentezinden sorumlu olan kolin asetil transferaz düzeyindeki azalma %58-90'dır. Mevcut ilaçlar hastalığın ilerlemesini durduramadığından, hastalığın temel nedenini hedef alan yeni ilaçlara büyük ihtiyaç vardır. Bu çalışmada asetilkolinesteraz inhibisyonu gösteren triazol-piridazinon türevi bileşikler sentezlenmiştir ve enzim inhibisyonları araştırılmıştır. Bileşik 6e, 0.049 ± 0.014 µM Ki değeri ile en güçlü inhibitör etkiyi göstermiştir (Takrin Ki= 0.226 ± 0.025 µM). Ayrıca sentezlenen tüm bileşikler için in-silico çalışmalar yapıldı.

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Cite This Article

Bozbey, İ., Önel, G. T., Türkmenoğlu, B., Gürsoy, Ş., Dilek, E. (2022). 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. Fabad Eczacılık Bilimler Dergisi, Cilt: 47 Sayı: 3, 355–368. https://doi.org/10.55262/fabadeczacilik.1128446

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