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

English (OpenAlex)

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.