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

Area of Science:

• Biochemistry
• Pharmacology
• Oncology

Background:

• Chemoresistance is a major obstacle in cancer therapy, often linked to cellular detoxification systems.
• Glutathione S-transferases P1 (GSTP1) isoenzyme inactivates anticancer drugs, contributing to chemoresistance.

Purpose of the Study:

• To identify novel inhibitors of GSTP1 to overcome chemoresistance.
• To screen quercetin derivatives for their potential to inhibit GSTP1.

Main Methods:

• In silico screening of quercetin derivatives for molecular properties, pharmacokinetics, and toxicity.
• Molecular docking and simulations of selected derivatives with GSTP1.
• Molecular dynamics simulations to assess complex stability.

Main Results:

• Quercetin 7-O-β-D-glucoside demonstrated strong binding affinity (-8.1 kcal/mol) to GSTP1.
• The compound exhibited favorable predicted pharmacokinetic properties and no significant toxicity.
• Molecular dynamics simulations confirmed the stability of the GSTP1-quercetin 7-O-β-D-glucoside complex.

Conclusions:

• Quercetin 7-O-β-D-glucoside is a promising lead candidate for combating cancer chemoresistance.
• Further experimental validation is required to confirm its therapeutic potential.