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

Year 2020, Volume: 9 Issue: 2, 644 - 654, 15.06.2020

Ayşe Tan

https://doi.org/10.17798/bitlisfen.644565

Cited By: 6

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

Thanks

Çalışmalarımda desteğini esirgemeyen sayın Yunus Kara’ya, sayın Samir Abbas Ali Noma’ya ve Sayın Burhan Ateş’e teşekkür ederim.

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

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