The Synthesis, Characterization and Molecular Docking Studies of Novel 1,2,3-Triazole Derivatives as Xanthine Oxidase Inhibitor

Abstract

In this study, the synthesis, characterization of novel 1,2,3-triazole compounds (4 and 5), investigation of their in vitro inhibition effects on xanthine oxidase and molecular docking studies were carried out. For this purpose, firstly; the target products (4 and 5) were synthesized by various chemical transformations starting from butadiene sulfone. All of the synthesized compounds were characterized by spectroscopic methods. In the second step; in vitro inhibition effects of compounds 4 and 5 on xanthine oxidase were investigated. According to the enzyme inhibition results, It was determined that compounds 4 (IC50 = 0.609 µM) and 5 (IC50 = 0.901 µM) showed stronger inhibition effect than allopurinol (IC50 = 1.143 µM), which is used as a drug for inhibition of xanthine oxidase. Finally, the binding modes of compounds 4 and 5 in the active part of xanthine oxidase (PDB ID:3NVY) were explained by molecular docking studies.

Keywords

• 1,2,3-triazole
• Xanthine oxidase
• 1,3-dipolar cycloaddition
• Molecular docking

Ksantin Oksidaz İnhibitörü Yeni 1,2,3-triazol Türevlerinin Sentezi, Karakterizasyonu ve Moleküler Doking Çalışmaları

Abstract

Bu çalışmada, yeni 1,2,3-triazol bileşiklerinin (4 ve 5) sentezi, karakterizasyonu, ksantin oksidaz enzimi üzerine in vitro inhibisyon etkilerinin incelenmesi ve moleküler doking çalışmaları gerçekleştirildi. Bu amaçla öncelikle; hedef ürünler (4 ve 5), bütadien sülfondan çıkılarak çeşitli kimyasal transformasyonlarla sentezlendi. Sentezlenen bütün bileşiklerin yapıları spektroskopik yöntemlerle aydınlatıldı. İkinci aşamada; 4 ve 5 bileşiklerinin ksantin oksidaz enzimi üzerine in vitro inhibisyon etkileri incelendi. Enzim inhibisyon sonuçlarına göre; 4 (IC₅₀ = 0.609 µM) ve 5 (IC₅₀ = 0.901 µM) bileşiklerinin, ksantin oksidaz enzim inhibisyonu için ilaç olarak kullanılan Allopurinol’den (IC₅₀ = 1.143 µM) daha güçlü inhibisyon etki gösterdiği tespit edildi. Son olarak; 4 ve 5 bileşiklerinin, ksantin oksidaz eziminin (PDB ID:3NVY) aktif kısmına bağlanma modları, moleküler doking çalışmaları ile açıklandı.

Keywords

• triazol
• moleküler doking
• dipolar sikloadisyon

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