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

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.

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