Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method

Year 2022, Volume: 12 Issue: 1, 88 - 105, 30.06.2022

Nuri Yorulmaz Hilal Öztürk Mustafa Durgun

https://doi.org/10.37094/adyujsci.1091227

Abstract

Molecular docking is a simulation technique that calculates the binding score of the molecules of interest to protein structures and visualizes the bond structure. It is a widely used technique for foresight because it helps to determine bond relationships between molecular structures before laboratory applications in the development of new drugs. ADME studies also provide clues for the determination of the molecules analyzed by the molecular docking method to be drug candidates. In this study, inhibition of CA IX and CA XII enzymes by sulfonamide derivatives synthesized in our previous study was investigated using molecular docking method. The CA enzyme family has an important role in the survival and spread of cancer cells. Therefore, we aimed to find new drug candidates that inhibit these enzymes. We found that the sulfonamide derivative named 6 binds to the active sites of both CA IX and CA XII enzymes with -7.44 kcal/mol and -6.39 kcal/mol energy, respectively, closest to the binding of the reference molecule acetazolamide. In addition, the compatibility of all compounds used in the study with drug-like properties was investigated using the ADME method. In conclusion, it can be said that the sulfonamide derivatives named 1-9 generally have the characteristic features of a drug (physicochemical and structural properties) and oral bioavailability.

Keywords

Molecular docking, ADME, CAIX, CAXII, Sulfonamide derivatives

Karbonik Anhidraz IX/XII'nin Potansiyel İnhibitörleri Olarak Bazı Sülfonamit Türevlerinin ADME ve Moleküler Yerleştirme Metodu ile Değerlendirilmesi

Abstract

Moleküler yerleştirme, ilgili moleküllerin protein yapılarına bağlanma enerjilerini hesaplayan ve bağ yapısını görselleştiren bir simülasyon tekniğidir. Çeşitli hastalıklara ilişkin yeni ilaçların keşfi ve geliştirilmesinde, laboratuvar uygulamalarından önce moleküler yapılar arasındaki bağlanmaları belirlemeye yardımcı olması sebebiyle, yaygın olarak kullanılan bir tekniktir. ADME çalışmaları da moleküler yerleştirme yöntemiyle analiz edilen moleküllerin ilaç adayı olma özelliklerinin belirlenmesinde ipuçları sağlamaktadır. Bu çalışmada, daha önceki çalışmamızda sentezlenen sülfonamit türevleri tarafından CA IX ve CA XII enzimlerinin inhibisyonu, moleküler yerleştirme yöntemi kullanılarak araştırılmıştır. Karbonik anhidraz (CA) enzim ailesi, kanser hücrelerinin hayatta kalmasında ve yayılmasında önemli bir role sahiptir. Bu nedenle bu enzimleri inhibe eden yeni ilaç adayları bulmayı amaçladık. 6 numaralı sülfonamit türevinin hem CA IX hem de CA XII enzimlerinin aktif bölgelerine sırasıyla -7,44 kcal/mol ve - 6,39 kcal/mol enerji ile referans molekül asetazolamitin (AZM) bağlanmasına en yakın şekilde bağlandığını bulduk. Ayrıca çalışmada kullanılan tüm bileşiklerin ilaç benzeri özelliklerle uyumluluğu ADME yöntemi kullanılarak araştırılmıştır. Sonuç olarak, 1-9 olarak adlandırılmış sülfonamit türevlerinin genel olarak bir ilacın karakteristik özelliklerine (fizikokimyasal ve yapısal özellikler) ve oral biyoyararlanıma sahip olduğu söylenebilir.

Keywords

Moleküler yerleştirme; ADME; CA IX; CA XII; Sülfonamit türevleri.

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