Yeni Tiyazolil-Hidrazin Türevlerinin Sentezi ve Asetilkolinesteraz (AChE) ve Bütirilkolinesteraz (BuChE) Aktivite Çalışmaları

Year 2022, Volume: 9 Issue: 1, 277 - 285, 30.06.2022

Ayşen Işık , Ulviye Acar Çevik , Tugba Ercetin , Ahmet Koçak

https://doi.org/10.35193/bseufbd.1017849

Abstract

Alzheimer hastalığı (AH), zamanla beyin hücrelerinin ölümüne bağlı olarak bilişsel işlevlerde azalma, hafıza kaybı ve bunama ile ilişkilendirilmiştir. Alzheimer hastalığının tedavisinde sınırlayıcı uygulamaların mevcut oluşu, hastalığın sağlık harcamalarında kanser ve kalp hastalıklardan sonra dünyada üçüncü sırada oluşu araştırmacıları AH üzerinde erken evrede tanıma ve yeni tedavi yöntemlerine yönlendirmektedir. Günümüzde kolinerjik anomalikler ile AH arasında doğrudan bir ilişki olduğu düşünülmektedir. Çalışmalar, asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) inhibisyonunun asetilkolin (ACh) seviyesinde meydana gelen artışların Alzheimer hastalığının başlangıç evrelerindeki bilişsel yetmezliği iyileştirebileceğini kanıtlamıştır. Dolayısıyla ACh düzeylerini arttırmak için uygulanacak en iyi metot ise, ACh’yi yıkan AChE veya BuChE enzimlerinin baskılanmasıdır. Dolayısıyla yapılan bu çalışmada, sübstitüe edilmiş tiyazolilhidrazin türevleri tasarlanmış, sentezlenmiş ve AH’ ye karşı asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BuChE) kolinesteraz enzimlerinin inhibisyon potansiyelleri araştırılmıştır. Hedef bileşiklerin yapıları 1H NMR/13C NMR analiz yöntemleri ile aydınlatılmıştır. Hedef bileşiklerin AChE ve BuChE enzimleri üzerindeki inhibisyon etkileri Ellman yöntemiile değerlendirilmiş ve hedef bileşiklerin enzim inhibisyon çalışmaları sonucunda 3d bileşiğinin orta düzeyde bütirilkolinesteraz enzimini inhibe ettiği tespit edilmiştir.

Keywords

Alzheimer Hastalığı, Tiyazolilhidrazin, Ellman Metot

Synthesis of Novel Thiazolyl-Hydrazine Derivatives and Activity Studies of Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE)

Abstract

Alzheimer's disease (AD) has been associated with ecreased cognitive function, memory loss, and dementia due to the death of brain cells over time. Existence of limiting practices in the treatment of AD, and the fact that the disease ranks third in health expenditures in the world after cancer and heart diseases, directs researchers to early diagnosis and new treatment methods on AD. Today, it is thought that there is a direct relationship between cholinergic abnormalities and AD. Studies have shown that acetylcholine (ACh) level increases due to acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition can improve cognitive impairment in the initial stages of Alzheimer's disease. The best method to increase these ACh levels is to suppress the AChE or BuChE enzymes that break down ACh. Therefore, in this study, substituted thiazolylhydrazine derivatives were designed, synthesized and their cholinesterase inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes against AD were investigated. The structures of the target compounds were illuminated by 1H NMR/13C NMR analysis methods. The effects of the target compounds on the on AChE and BuChE enzymes were evaluated using the Ellman process and as a result of the enzyme inhibiton studies of the target compounds, it was determined that the 3d compound showed moderate butyrylcholinesterase activity.

Keywords

Alzheimer, Thiazolylhydrazine, Ellman Method

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