Antityrosinase Activities and in silico ADME Properties of Fluorine-containing 1,2,4-triazole-5-on Derivatives

Abstract

Bu çalışmada, flor içeren 1,2,4-triazol-5-on türevlerinin (2a-b, 3a-b, 4a-d, 5a-b, 6a-b, 7a-b, 8a-b ve 9a-b) klinik öneme sahip tirosinaz enziminin aktivitesi üzerine inhibisyon potansiyelleri incelenmiştir. Moleküllerin IC50 değerleri belirlenmiştir. Moleküller arasında en iyi inhibisyon özelliği gösteren molekülün inhibisyon türü ve Ki değeri hesaplanmıştır. Ticari olarak temin edilen mantar tirosinaz için optimum reaksiyon şartları belirlendikten sonra, kinetik çalışmalar yapılarak en düşük IC50 değerine sahip molekülün 8b olduğu tespit edilmiştir. Referans inhibitör molekül olarak kullanılan kojik aside (IC50=45,7±0,9 µM) göre 8a-b, 9a-b (IC50 değerleri sırasıyla 32,2±0,7 µM; 22,9±0,6 µM; 22,8±0,5 µM; 23,8±0,6 µM) moleküllerinin tirosinaz aktivitesi üzerinde oldukça etkili inbitör özelliğine sahip olduğu tespit edilmiştir. 8b molekülü için inhibisyon türü nonkompetetif olarak belirlenmiş ve Ki değeri 6,09±0,12 µM olarak hesaplanmıştır. Ayrıca tüm moleküllerin ADME özellikleri de incelenmiş olup, her bir molekülün ilaç aday molekülü olarak yüksek bir potansiyele sahip olduğu tespit edilmiştir. Bu sonuçlar neticesinde 8a-b ve 9a-b molekülleri, tirosinaz aktivitesine karşı oldukça etkili ve umut verici inhibitör bileşikler olarak kabul edilebilir.

Keywords

• ADME özellikleri
• antitirosinaz aktivite
• triazoller

Thanks

As the authors, we thank Olcay BEKIRCAN for the synthesis and supply of the materials used in this study.

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