Inhibitory Potential of Quercetin Derivatives for GSTP-1 Enzyme: Molecular Docking Study of Methoxylated Derivatives

Öz

Glutathione S-transferases (GSTs) are an important enzyme class involved in detoxification processes. The overactivation of the GSTP-1 isozyme, particularly in cancer cells, leads to the development of resistance to chemotherapy drugs. Therefore, GSTP-1 inhibitors are gaining importance as potential therapeutic targets in cancer treatment. In this study, we aimed to investigate whether quercetin and its derivatives have inhibitory potential on the GSTP-1 enzyme through molecular docking methods. The crystal structure of the GSTP-1 enzyme was obtained from the Protein Data Bank (PDB ID: 2GSS), and molecular docking studies were conducted using the AutoDock Vina 1.2.5 program. Quercetin derivatives and ethacrynic acid were used as ligands, and the binding energies of these compounds to GSTP-1 were calculated, comparing their inhibitory potentials. Additionally, hydrogen bond interactions were examined alongside binding energies. The binding energy of ethacrynic acid was found to be -6.7 kcal/mol, while quercetin had a binding energy of -7.2 kcal/mol, 3-O-methylquercetin -7.3 kcal/mol, 4-O-methylquercetin -7.2 kcal/mol, and 7-O-methylquercetin -7.5 kcal/mol. These results indicate that the strongest inhibitory effect was exhibited by 7-O-methylquercetin. Furthermore, strong hydrogen bond interactions were observed between quercetin derivatives and GSTP-1. These findings suggest that quercetin derivatives have the potential to inhibit the GSTP-1 enzyme and may pave the way for new strategies in cancer treatment.

Anahtar Kelimeler

• Cancer
• GSTP-1
• Quercetin
• Molecular docking

GSTP-1 Enzimi İçin Kuersetin Türevlerinin İnhibitör Potansiyeli: Metoksillenmiş Türevlerin Moleküler Docking Çalışması

Öz

Glutatyon S-transferazlar (GST'ler), detoksifikasyon süreçlerinde rol oynayan önemli bir enzim sınıfıdır. Özellikle GSTP-1 izozimlerinin kanser hücrelerindeki aşırı aktivasyonu, bu hücrelerin kemoterapi ilaçlarına karşı direnç geliştirmesine neden olmaktadır. Bu nedenle GSTP-1 inhibitörleri, kanser tedavisinde potansiyel bir terapötik hedef olarak önem kazanmaktadır. Bu çalışmada, kuersetin ve türevlerinin GSTP-1 enzimi üzerinde inhibitör potansiyele sahip olup olmadığını moleküler yerleştirme (docking) yöntemiyle araştırmayı amaçladık. Çalışmada, GSTP-1 enziminin kristal yapısı Protein Veri Bankası'ndan (PDB ID: 2GSS) elde edilmiştir ve moleküler yerleştirme çalışmaları AutoDock Vina 1.2.5 programı kullanılarak gerçekleştirilmiştir. Kuersetin türevleri ve etakrinik asit ligand olarak kullanılmış ve bu bileşiklerin GSTP-1 ile bağlanma enerjileri hesaplanarak inhibitör potansiyelleri karşılaştırılmıştır. Ayrıca, bağlanma enerjilerinin yanı sıra hidrojen bağı etkileşimleri de incelenmiştir. Etakrinik asidin bağlanma enerjisi -6.7 kcal/mol olarak bulunurken, kuersetinin -7.2 kcal/mol, 3-O-metilkuersetinin -7.3 kcal/mol, 4-O-metilkuersetinin -7.2 kcal/mol ve 7-O-metilkuersetinin -7.5 kcal/mol bağlanma enerjilerine sahip olduğu belirlenmiştir. Sonuçlar, en güçlü inhibitör etkinin 7-O-metilkuersetin tarafından gösterildiğini ortaya koymaktadır. Ayrıca, kuersetin türevlerinin GSTP-1 ile güçlü hidrojen bağı etkileşimleri gösterdiği tespit edilmiştir. Bu bulgular, kuersetin türevlerinin GSTP-1 enzimi inhibisyon potansiyeline sahip olduğunu ve kanser tedavisinde yeni stratejilere kapı aralayabileceğini işaret etmektedir.

Anahtar Kelimeler

• Kanser
• GSTP-1
• Kuersetin
• Moleküler yerleştirme

Kaynakça

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