GLUTATYON S-TRANSFERAZ PI-1 İZOENZİMİNİN POTANSİYEL BİR İNHİBİTÖRÜ OLARAK GRAFEN KUANTUM NOKTALARI VE TÜREVLERİ: HESAPLAMALI BİR ÇALIŞMA

Abstract

Amaç: Glutatyon S-Transferazlar (GST'ler) adı verilen Faz II detoksifikasyon enzimleri vücudumuzu ksenobiyotiklerin zararlı etkilerinden korur. GSTP1 izoenzimi yalnızca toksik maddeleri detoksifiye etmekle kalmaz, aynı zamanda kanser tedavisi direncine de katkıda bulunur. En erken ve en etkili GST inhibitörü etakrinik asittir (EA). Bu çalışma, GSTP1'in olası bir inhibitörü fikrini sunmak için moleküler yerleştirme analizini kullanarak antikanser araştırmalarında faydalı olduğu gösterilen EA ile grafen kuantum noktalarını (GQD'ler) karşılaştırmaktadır. Gereç ve Yöntem: Gaussview 5.0 yazılımı kullanılarak, yoğunluk fonksiyonel teorisi (DFT) yöntemi GQDs bileşiği üzerindeki teorik hesaplamalara uygulandı. Geometriyi iyileştirmek için Gaussian 09 uygulaması kullanıldı. Bileşiklerin reaktif bölgelerini belirlemek için moleküler elektrostatik potansiyel (MEP) hesaplamaları kullanıldı. Optimize edilmiş EA ve GQDs molekülü ile GSTP1 arasında moleküler yerleştirme çalışmaları yürütmek için PyRx Tools ve AutoDock Vina yazılımı kullanıldı. Reseptör-ligand etkileşimleri Discover Studio Visualizer 4.0 kullanılarak görselleştirildi. Sonuç ve Tartışma: GQD’lar, EA’da olduğu gibi GSTP1’in H Site rezidüleriyle etkileşimde olduğu bulundu. Ancak, elektrofiliklik kapasitesi EA’ya göre çok daha düşüktü. Yüzey modifikasyonları ile elektrofilikliği artırılarak, GSTP1 inhibitörü olabileceği düşüncesindeyiz.

Keywords

• Glutatyon S-transferaz
• grafen kuantum noktaları
• moleküler kenetlenme
• yoğunluk fonksiyonel teorisi

GRAPHENE QUANTUM DOTS AND ITS DERIVATIVES AS A POTENTIAL INHIBITOR OF GLUTATHIONE S-TRANSFERASE PI-1 ISOENZYME: A COMPUTATIONAL STUDY

Abstract

Objective: Phase II detoxification enzymes called Glutathione S-Transferases (GSTs) protect our bodies from the harmful effects of xenobiotics. The GSTP1 isoenzyme not only detoxifies toxic substances but also contributes to cancer treatment resistance. The earliest and most potent GST inhibitor is ethacrynic acid (EA). This work compares graphene quantum dots (GQDs) with EA that has been shown to be beneficial in anticancer investigations, using molecular docking analysis in order to offer the idea of a possible inhibitor of GSTP1. Material and Method: The density functional theory (DFT) method was applied to theoretical calculations on the GQDs compound using Gaussview 5.0 software. The application Gaussian 09 was used to refine the geometry. Calculations of molecular electrostatic potential (MEP) were used to identify the compounds' reactive sites. PyRx Tools and AutoDock Vina software were used to conduct molecular docking studies between the optimized EA and the GQDs molecule with GSTP1. The receptor-ligand interactions were visualized using Discover Studio Visualizer 4.0. Result and Discussion: GQDs were found to interact with the H Site residues of GSTP1, as in EA. However, their electrophilicity was much lower than EA. We think that they can be GSTP1 inhibitors by increasing their electrophilicity with surface modifications.

Keywords

• Density functional theory
• glutathione S-transferase
• graphene quantum dots
• molecular docking

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