Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies

Year 2023, Volume: 16 Issue: 2, 345 - 356, 31.08.2023

Fulya Öz Tuncay , Ümmühan Çakmak

https://doi.org/10.18185/erzifbed.1216717

Abstract

Diabetes Mellitus (DM), kan glukoz seviyesinin yükseldiği, postprandiyal hiperglisemiye neden olan, böbrek yetmezliği, körlük, kardiyovasküler hastalıklar ve sinir hasarı gibi pek çok sekonder probleme neden olan metabolik bir hastalıktır. α-Amilaz ve α-glukozidaz doğrudan tip II DM ile ilgilidir ve bu enzimlerin inhibitörleri nişasta sindirimini inhibe edebildiğinden DM tedavisinde yaygın olarak kullanılmaktadır. Bu çalışmada flor içeren 1,2,4-triazol-5-on türevlerinin (4a-d, 6a-b, 7a-b, 8a-b) α-amilaz ve α-glukozidaza karşı inhibisyon potansiyelleri araştırıldı. Tüm moleküller, akarboz standardı kontrolü altında (IC50 = 411,3 ± 6,4 uM) 185,2 ± 3,4 ila 535,6 ± 5,5 μM arasında değişen farklı oranlarda α-amilaz inhibisyonu sergiledi; α-glukozidaz varlığında ise, pozitif kontrol akarboza kıyasla IC50 değerleri 205,0 ± 3,8 ila 803,2 ± 10,3 μM arasında değişim gösterdi (IC50 = 252,0 ± 4,8 μM). 10 farklı inhibitör molekülü arasında 4c'nin her iki durumda da mükemmel inhibe edici potansiyele sahip olduğu tespit edildi ve a-amilaz ve a-glukozidazın inhibisyon türü kinetik çalışmalarla değerlendirildi. Ayrıca SwissADME yazılımı kullanılarak 4c molekülünün fizikokimyasal ve farmakokinetik özellikleri hesaplandı. Mevcut araştırmanın sonuçları, tip II DM'nin tedavisi için umut vaat eden bir aday olarak 4c molekülünün potansiyelini desteklemektedir.

Keywords

α-Amylase, α-glucosidase, inhibition kinetics, pharmacokinetics, triazoles

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