Exploring the GSTP1 inhibition potential of photosensitizer compounds for enhanced cancer treatment in photodynamic therapy.

Photodynamic therapy (PDT) has gained considerable attention in cancer treatment due to its non-invasive nature and the ability of photosensitizers to generate reactive oxygen species upon light activation, leading to tumor destruction. Glutathione S-transferase P1 (GSTP1) is a key enzyme in chemotherapy resistance, often overexpressed in various cancers, and its inhibition of GSTP1 presents a promising strategy to enhance cancer treatment. This study is aimed at assessing the potential of prominent photosensitizers as GSTP1 inhibitors through molecular docking analysis to strengthen the efficacy of PDT. The photosensitizers were docked into the active site of GSTP1, and their binding affinities, inhibition constants (Ki), and molecular interactions were assessed. Among the tested photosensitizers, zinc phthalocyanine, hypericin, and temoporfin emerged as the top candidates, exhibiting binding energies of - 10.8, - 10.2, and - 9.8 kcal/mol, along with Ki values of 0.012, 0.033, and 0.064 µM, respectively. These compounds outperformed the reference inhibitor ethacrynic acid, which had a binding energy of - 6.6 kcal/mol and a Ki of 14.35 µM. These findings suggest that the dual action of these photosensitizers provides a promising strategy for combating cancer and overcoming treatment resistance.