Yıl: 2022 Cilt: 47 Sayı: 3 Sayfa Aralığı: 355 - 368 Metin Dili: İngilizce DOI: 10.55262/fabadeczacilik.1128446 İndeks Tarihi: 25-11-2022

Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays

Öz:
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.
Anahtar Kelime:

1,2,3-Triazol Uygulaması Yeni Anti-Alzheimer (P-Tolil)-3(2H)- Piridazinon Türevleri: Sentez Çalışmaları, in vitro ve in siliko Analizleri

Öz:
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 siliko çalışmalar yapıldı.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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APA Bozbey Merde İ, Taşkor Önel G, TÜRKMENOĞLU B, GÜRSOY Ş, Dilek E (2022). Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. , 355 - 368. 10.55262/fabadeczacilik.1128446
Chicago Bozbey Merde İrem,Taşkor Önel Gülce,TÜRKMENOĞLU BURÇİN,GÜRSOY ŞULE,Dilek Esra Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. (2022): 355 - 368. 10.55262/fabadeczacilik.1128446
MLA Bozbey Merde İrem,Taşkor Önel Gülce,TÜRKMENOĞLU BURÇİN,GÜRSOY ŞULE,Dilek Esra Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. , 2022, ss.355 - 368. 10.55262/fabadeczacilik.1128446
AMA Bozbey Merde İ,Taşkor Önel G,TÜRKMENOĞLU B,GÜRSOY Ş,Dilek E Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. . 2022; 355 - 368. 10.55262/fabadeczacilik.1128446
Vancouver Bozbey Merde İ,Taşkor Önel G,TÜRKMENOĞLU B,GÜRSOY Ş,Dilek E Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. . 2022; 355 - 368. 10.55262/fabadeczacilik.1128446
IEEE Bozbey Merde İ,Taşkor Önel G,TÜRKMENOĞLU B,GÜRSOY Ş,Dilek E "Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays." , ss.355 - 368, 2022. 10.55262/fabadeczacilik.1128446
ISNAD Bozbey Merde, İrem vd. "Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays". (2022), 355-368. https://doi.org/10.55262/fabadeczacilik.1128446
APA Bozbey Merde İ, Taşkor Önel G, TÜRKMENOĞLU B, GÜRSOY Ş, Dilek E (2022). Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. FABAD Journal of Pharmaceutical Sciences, 47(3), 355 - 368. 10.55262/fabadeczacilik.1128446
Chicago Bozbey Merde İrem,Taşkor Önel Gülce,TÜRKMENOĞLU BURÇİN,GÜRSOY ŞULE,Dilek Esra Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. FABAD Journal of Pharmaceutical Sciences 47, no.3 (2022): 355 - 368. 10.55262/fabadeczacilik.1128446
MLA Bozbey Merde İrem,Taşkor Önel Gülce,TÜRKMENOĞLU BURÇİN,GÜRSOY ŞULE,Dilek Esra Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. FABAD Journal of Pharmaceutical Sciences, vol.47, no.3, 2022, ss.355 - 368. 10.55262/fabadeczacilik.1128446
AMA Bozbey Merde İ,Taşkor Önel G,TÜRKMENOĞLU B,GÜRSOY Ş,Dilek E Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. FABAD Journal of Pharmaceutical Sciences. 2022; 47(3): 355 - 368. 10.55262/fabadeczacilik.1128446
Vancouver Bozbey Merde İ,Taşkor Önel G,TÜRKMENOĞLU B,GÜRSOY Ş,Dilek E Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays. FABAD Journal of Pharmaceutical Sciences. 2022; 47(3): 355 - 368. 10.55262/fabadeczacilik.1128446
IEEE Bozbey Merde İ,Taşkor Önel G,TÜRKMENOĞLU B,GÜRSOY Ş,Dilek E "Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays." FABAD Journal of Pharmaceutical Sciences, 47, ss.355 - 368, 2022. 10.55262/fabadeczacilik.1128446
ISNAD Bozbey Merde, İrem vd. "Novel (p-Tolyl)-3(2H)-Pyridazinone Derivatives Containing Substituted-1,2,3-Triazole Moiety as New AntiAlzheimer Agents: Synthesis, In vitro and In silico Assays". FABAD Journal of Pharmaceutical Sciences 47/3 (2022), 355-368. https://doi.org/10.55262/fabadeczacilik.1128446