Netting into the Sophoretin pool: An approach to trace GSTP1 inhibitors for reversing chemoresistance

Chemoresistance, a significant challenge in cancer treatment, is often associated with the cellular glutathionerelated detoxification system. The GSTP1 isoenzyme (glutathione S-transferases) plays a critical role in the cytoplasmic inactivation of anticancer drugs. This suggests the identification of GSTP1 inhibitors to combat chemoresistance. We screened Sophoretin (also called quercetin) derivatives for molecular properties, pharmacokinetics, and toxicity profiles. Following that, we conducted molecular docking and simulations between selected derivatives and GSTP1. The best-docked complex, GSTP1-quercetin 7-O-beta-D-glucoside, exhibited a binding affinity of -8.1 kcal/mol, with no predicted toxicity and good pharmacokinetic properties. Molecular dynamics simulations confirmed the stability of this complex. Quercetin 7-O-beta-D-glucoside shows promise as a lead candidate for addressing chemoresistance in cancer patients, although further experimental studies are needed to validate its efficacy and therapeutic potential.

Automated summary

Chemoresistance, a major challenge in cancer treatment, is associated with the cellular glutathione-related detoxification system. A study has identified GSTP1 enzyme as critical in the inactivation of anticancer drugs and suggests the need for GSTP1 inhibitors to combat chemoresistance. Through molecular docking and simulations, the study found that quercetin 7-O-beta-D-glucoside showed promise as a potential candidate for addressing chemoresistance in cancer patients.