Synthesis, characterization, molecular docking and cholinesterase inhibition studies of new thiazole-hydrazinyl derivatives

Year 2023, Volume: 25 Issue: 2, 516 - 525, 07.07.2023

Ulviye Acar Çevik , Ayşen Işık , İsmail Çelik , Tugba Ercetin

https://doi.org/10.25092/baunfbed.1113229

Abstract

Alzheimer's disease (AD) results from the destruction or loss of cholinergic cells in the brain that produce or use acetylcholine. Therefore, the main treatment strategy for AD is to increase the level of acetylcholine in the brain. In this study, the synthesis of new thiazole-hydrazinyl derivatives as cholinesterase inhibitors was carried out. The structures of the synthesized compounds were elucidated by 1H-NMR and 13C-NMR data. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of synthesized target compounds were evaluated using the Ellman method. Molecular docking was performed with Autodock Vina. All synthesized compounds were found to exhibit low activity against AChE. Among the synthesized compounds, only compound 3j was found to selectively inhibit BuChE. According to data from molecular docking, compound 3j formed 10.0 kcal/mol interaction energy at the BuChE active site and key pi-pi staked interactions with Trp82. In conclusion, this study guides the development of selective BuChE inhibitory agents for the treatment of Alzheimer's disease.

Keywords

Thiazole, Hydrazine, Acetylcholinesterase, Butyrylcholinesterase, Docking.

Yeni tiyazol-hidrazinil türevlerinin sentezi, karakterizasyonu, moleküler doking ve kolinesteraz inhibisyon çalışmaları

Abstract

Alzheimer hastalığı (AD), beyinde asetilkolin üreten veya kullanan kolinerjik hücrelerin yıkımı veya kaybından kaynaklanmaktadır. Bundan dolayı, AD için ana tedavi stratejisi beyindeki asetilkolin seviyesini arttırmaktır. Bu çalışmada, kolinesteraz inhibitörleri olarak yeni tiyazol-hidrazinil türevlerinin sentezi gerçekleştirilmiştir. Sentezlenen bileşiklerin yapısı 1H-NMR ve 13C-NMR verileri ile aydınlatılmıştır. Sentezlenen hedef bileşiklerin asetilkolinesteraz (AChE) ve butirilkolinesteraz (BChE) inhibitör etkileri Ellman yöntemi kullanılarak değerlendirilmiştir. Moleküler doking çalışması Autodock Vina ile yapılmıştır. Sentezlenen bütün bileşiklerin AChE karşı düşük etkinlik sergilediği bulunmuştur. Sentezlenen bileşikler arasından sadece bileşik 3j seçici olarak BuChE inhibe ettiği bulunmuştur. Dokingden elde edilen verilere göre bileşik 3j, BuChE aktif sitesinde 10.0 kcal/mol etkileşim enerjisi ve Trp82 ile anahtar pi-pi staked etkileşimleri oluşturmuştur. Sonuç olarak, bu çalışma Alzheimer hastalığının tedavisinde seçici BuChE inhibitörü ajan geliştirmede yol göstericidir.

Keywords

Tiyazol, Hidrazin, Asetilkolinesteraz, Bütirilkolinesteraz, Doking.

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