Stigmasterol, Sesamin ve Pinosilvin'in GSTP1 İnhibisyon Potansiyellerinin ve Farmakokinetik Özelliklerinin Değerlendirilmesi

Yıl 2025, Cilt: 7 Sayı: 2, 154 - 163, 23.06.2025

Nihan Küçük , Mehmet Özcan

https://doi.org/10.52827/hititmedj.1599510

Öz

Amaç: Kanser tedavisinde ilaç direncini etkileyen önemli bir hedef olan Glutatyon S-transferaz P1 (GSTP1), detoksifikasyon ve reaktif oksijen türlerinin regülasyonundaki rolü nedeniyle kritik bir konudur. Bu çalışmada, doğal bileşiklerin (bakuchiol, sesamin, hidroksitirosol, stigmasterol ve pinosilvin) GSTP1’e karşı inhibitör potansiyelleri ve ADME (Absorpsiyon, metabolizma, dağılım, eliminasyon) profilleri değerlendirilmiştir.
Gereç ve Yöntem: Moleküler kenetleme simülasyonları ve absorpsiyon, metabolizma, dağılım, eliminasyon profillemesi kullanılarak, bu bileşiklerin inhibitör etkinlikleri referans inhibitör olan etakrinik asit ile karşılaştırılmıştır.
Bulgular: Kenetleme simülasyonları, stigmasterol (-9,2 kcal/mol) ve sesaminin (-8,2 kcal/mol) en güçlü bağlanma afinitelerini sergilediğini, ardından pinosilvin’in (-7,1 kcal/mol) inhibisyon potansiyelinde etakrinik asidi (-6,7 kcal/mol) geride bıraktığını gösterdi. Absorpsiyon, metabolizma, dağılım ve eliminasyon analizi, çözünürlük ve enzim etkileşimi riskleri belirtmiş olsa da sesamin ve pinosylvin için olumlu farmakokinetik özellikleri vurguladı.
Sonuç: Bu çalışma, Glutatyon S-transferaz P1 aracılı ilaç direncini hedef alarak, bitki kaynaklı bileşiklerin potansiyelini vurgulamaktadır. Bu tür yaklaşımlar, kanser tedavisinde yeni ve etkili stratejiler geliştirilmesine olanak sağlayabilir.

Anahtar Kelimeler

ADME profillemesi , fitokimyasallar , GSTP1 , ilaç direnci , kanser tedavisi , moleküler yerleştirme

Evaluation of GSTP1 Inhibition Potentials and Pharmacokinetic Properties of Stigmasterol, Sesamin, and Pinosylvin

Öz

Objective: Glutathione S-transferase P1 (GSTP1), an important target affecting drug resistance in cancer treatment, is a critical issue due to its role in detoxifying and regulating reactive oxygen species. This study evaluated the inhibitory potentials of natural compounds (bakuchiol, sesamin, hydroxytyrosol, stigmasterol, and pinosylvin) against Glutathione S-transferase P1 and their absorption, metabolism, distribution, and elimination (ADME) profiles.
Material and Method: The inhibitory activities of these compounds were compared with those of the reference inhibitor, etacrynic acid, using molecular docking simulations and absorption, metabolism, distribution, and elimination profiling.
Results: Docking simulations showed that stigmasterol (-9.2 kcal/mol) and sesamin (-8.2 kcal/mol) exhibited the most potent binding affinities, followed by pinosylvin (-7.1 kcal/mol), surpassing etacrynic acid (-6.7 kcal/mol) in inhibition potential. Although the absorption, metabolism, distribution, and elimination analysis indicated risks related to solubility and enzyme interactions, it highlighted favorable pharmacokinetic properties for sesamin and pinosylvin.
Conclusion: This study emphasizes the potential of plant-derived compounds by targeting Glutathione S-transferase P1-mediated drug resistance. Such approaches may enable the development of new and effective strategies in cancer treatment.

Anahtar Kelimeler

ADME profiling , cancer therapy , drug resistance , GSTP1 , molecular docking , phytochemicals

Etik Beyan

ETİK BEYAN Bu çalışmanın yazarları olarak; - Araştırma ve yayın etiği ilkelerine uyulduğunu, - Tüm verilerin gerçek ve özgün olduğunu, - Dijital ve basılı tüm kaynaklara bilimsel kurallara uygun atıf yapıldığını, - Herhangi bir çıkar çatışmasının olmadığını, - Finansal destek alınmadığını beyan ederiz.

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