Structure-Based Virtual Screening of Plant-Derived Flavonoids as Putative GLUT9 Binders with Antioxidant Properties

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Hyperuricemia, a condition affecting 20% of adults globally, is the main cause of gout.
• Glucose transporter 9 (GLUT9) is crucial for renal urate reabsorption and a key therapeutic target for hyperuricemia.

Purpose of the Study:

• To identify novel flavonoid compounds that bind to GLUT9 using an integrated computational and experimental approach.
• To evaluate the binding affinity, antioxidant activity, and drug-like properties of identified flavonoids.

Main Methods:

• Molecular docking and molecular dynamics (MD) simulations against human GLUT9.
• ADMET prediction, antioxidant assays (DPPH, ABTS, FRAP), and Density Functional Theory (DFT) calculations.
• Evaluation of eight structurally diverse flavonoids for their binding and biological properties.

Main Results:

• All tested flavonoids showed favorable binding affinities (-7.67 to -9.10 kcal/mol) to GLUT9.
• Epigallocatechin gallate (EGCG) exhibited the highest binding affinity and potent antioxidant activity, surpassing ascorbic acid.
• Chrysin demonstrated strong GLUT9 binding with favorable drug-like properties, despite lower antioxidant capacity.

Conclusions:

• EGCG and chrysin are promising candidates for hyperuricemia treatment due to their favorable GLUT9 binding profiles.
• Further functional and pharmacokinetic studies are warranted to optimize EGCG and chrysin for therapeutic applications.