Novel 1,2,3-Triazole Compounds Containing Different Amine Groups: Synthesis, Characterization and in Silico Studies on Xanthine Oxidase

Year 2022, Volume: 22 Issue: 3, 508 - 516, 30.06.2022

Ayşe Tan

https://doi.org/10.35414/akufemubid.1105960

Abstract

In this study, novel 1,2,3-triazole derivatives containing different amine subunits 16(a-c) and 17(a-c) were synthesized and characterized by FT-IR, HRMS, 1H, and 13C NMR analyses. The interactions with xanthine oxidase (XO) enzyme of these compounds were investigated with molecular docking studies. The obtained results were compared with molecular docking studies of allopurinol and febuxostat, which are the XO inhibitors. All target compounds demonstrated better binding energies than allopurinol in the interaction with the XO. On the other hand, 16a and 17a exhibited better binding affinities than febuxostat. The best binding energy values of the target compounds, allopurinol, and febuxostat vary between -6.1 and 9.84 kcal/mol. In this case, the target compounds may show better activity than allopurinol against the XO in vitro enzyme-inhibition studies. Additionally, compounds 16a and 17a may show better activities than febuxostat, as well. Finally, in silico ADME and toxicity studies for all target compounds were performed. The ADME results suggested suitable drug-likeness values for the compounds. Regarding toxicity, the compounds are predicted to be safe in terms of mutagenicity and tumorigenicity.

Keywords

Xanthine oxidase, 1,2,3-triazole, Allopurinol, Febuxostat, ADMET, Molecular docking

Supporting Institution

Muş Alparslan Üniversitesi

Project Number

BAP-21-TBMY-4901-01

Thanks

The author thanks to Mus Alparslan University

Farklı Amin Grupları İçeren Yeni 1,2,3-Triazol bileşikleri: Sentez, Karakterizasyon ve Ksantin Oksidaz üzerine in Siliko Çalışmalar

Abstract

Bu çalışmada, farklı amin alt birimleri içeren yeni 1,2,3-triazol türevleri 16(a-c) ve 17(a-c) sentezlendi ve FT-IR, HRMS, 1H, ve 13C NMR analizleri ile yapıları karakterize edildi. Bu bileşiklerin ksantin oksidaz (XO) enzimi ile etkileşimleri moleküler yerleştirme çalışmaları ile incelendi. Elde edilen sonuçlar, XO inhibitörleri olarak bilinen allopurinol ve febuksostat’in moleküler yerleştirme çalışmaları ile karşılaştırıldı. Hedef bileşikler, XO ile etkileşimlerde allopurinolden daha iyi bağlanma enerjileri gösterdi. Diğer taraftan, 16a ve 17a bileşikleri, febuksostat’tan daha iyi bağlanma affiniteleri sergiledi. Hedef bileşikleri, allopurinol ve febuksostatın en iyi bağlanma enerjisi değerleri -6.1 ile 9.84 kcal/mol arasında değişmektedir. Bu durumda, hedef bileşiklerinin in vitro enzim inhibisyon çalışmalarında XO'ya karşı allopurinolden daha iyi aktivite göstermesi olasıdır. Ayrıca, 16a ve 17a bileşikleri de febuksostattan daha iyi aktivite gösterebilir. Son olarak, tüm hedef bileşikler için in siliko ADME ve toksisite çalışmaları yapılmıştır. ADME sonuçları, bileşikler için kabul edilebilir ilaç benzerlik değerleri önerdi. Toksisite ile ilgili olarak, tüm bileşiklerin mutajenite ve tümörijenite açısından güvenli olduğu tahmin edilmektedir.

Keywords

Ksantin oksidaz, 1,2,3-triazol, Allopurinol, Febuksostat, ADMET, Moleküler yerleştirme

Project Number

BAP-21-TBMY-4901-01

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