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

Abstract

Chemoresistance, a significant challenge in cancer treatment, is often associated with the cellular glutathione-related 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-β-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-β-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.

Keywords: Chemoresistance; GSTP1 inhibitors; Molecular docking; Molecular dynamics; Quercetin derivatives; Sophoretin derivatives.