Diyabet Hastalığının Tedavisinde Kullanılabilecek Alfa-Amilaz İnhibitörü Olarak Kuersetin ve Umbelliferonun Etkisinin In Silico Kanıtı

Year 2022, Volume: 22 Issue: 3, 202 - 216, 23.12.2022

Ergin Murat Altuner

https://doi.org/10.17475/kastorman.1215281

Cited By: 3

Abstract

Çalışmanın amacı: Bu çalışmanın amacı, diyabet tedavisinde önemli α-amilaz inhibitörü olarak, kuersetin ve umbelliferonun potansiyel kullanımına ilişkin in silico kanıtları ortaya koymaktır.
Materyal ve yöntem: Kuersetin, umbelliferon ve ticari bir α-amilaz inhibitörü olan akarboz'un alfa - amilaza bağlanması sırasındaki olası konformasyonları ve yönelimleri taranmadan önce, enzimin potansiyel aktif bölgeleri CASTp 3.0 sunucusu tarafından tahmin ve analiz edilmiştir. Bu bileşiklerin potansiyel aktif bölgelerle 3D etkileşimleri ve bağlanma enerjilerini elde etmek için moleküler kenetlenme (docking) analizi Auto Dock Tools v.1.5.6 kullanılarak yapılmıştır. Ayrıca etkileşim skorları iGEMDOCK v.2.1 ile hesaplanmıştır. Aktif bölgelerdeki etkileşimleri açıkça gösteren 2D enzim-inhibitör etkileşimleri LigPlot+ v.2.2 ile analiz edilmiştir. Kuersetin ve umbelliferonun ilaç benzerliği özellikleri DruLiTo yazılımı ve SWISSADME sunucusu tarafından akarboz ile karşılaştırılmıştır. Bileşiklerin farmakokinetik özelliklerini gösteren absorpsiyon, dağılım, metabolizma, boşaltım ve toksisite (ADMET) skorları ADMETLab, admetSAR ve PreADMET sunucuları kullanılarak analiz edilmiştir.
Temel sonuçlar: Sonuç olarak, kuersetin ve umbelliferonun α-amilaz inhibitör aktivitesi ve bunların kullanım potansiyelleri in silico kanıtlanmıştır.
Araştırma vurguları: Çalışmanın sonuçları, kuersetin ve umbelliferonun diyabet tedavisinde olası bir tıbbi kullanıma sahip olabileceğini açıkça ortaya koymaktadır

Keywords

Kuersetin, Umbelliferon, Akarboz, Alfa Amilaz, İnhibitör, Moleküler Kenetlenme, ADMET

In Silico Proof of the Effect of Quercetin and Umbelliferone as Alpha-Amylase Inhibitors, Which Can Be Used in the Treatment of Diabetes

Abstract

Aim of study: The aim of this study is to show the in silico evidences about the potential use of quercetin and umbelliferone as α-amylase inhibitors, which is important for the treatment of diabetes.
Material and methods: The possible conformations and orientations of quercetin, umbelliferone, and acarbose, in binding to the active sites of alpha-amylase, were analysed by CASTp server. The molecular dockings of these compounds to the potential active site were performed by AutoDock Tools to obtain 3D interactions and binding energies. In addition, the interaction scores were calculated by iGEMDOCK. The 2D enzyme-inhibitor interactions, which clearly show the interactions at the active sites, were analysed by LigPlot+. The drug-likeness properties of quercetin and umbelliferone were compared to acarbose by DruLiTo software and SWISSADME server. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) scores, which present the pharmacokinetic properties of the compounds were analysed by ADMETLab, admetSAR, and PreADMET servers
Main results: As a result, the α-amylase inhibitor activity and the potential use of quercetin and umbelliferone were proved in silico.
Highlights: The results of the study clearly put forward that quercetin and umbelliferone could have possible medicinal use in the treatment of diabetes

Keywords

Quercetin, Umbelliferone, Acarbose, Alpha-Amylase, Inhibitor, Molecular Docking, ADMET

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