What question did this study set out to answer?

This research aims to assess the anti-breast cancer potential of resveratrol and quercetin derivatives using computational methods.

May 28, 2026Open Access

Identification of promising resveratrol and quercetin derivatives as breast Cancer therapeutics via computational approaches

Key Points

This research aims to assess the anti-breast cancer potential of resveratrol and quercetin derivatives using computational methods.
Conducted molecular docking and ADMET predictions on 25 derivatives against four protein targets.
Performed 300 ns molecular dynamics simulations to examine ligand-protein interactions.
Calculated binding affinities and toxicity risks based on lipophilicity and drug-likeness properties.
Compound 22 showed a binding free energy of ΔG = −123.76 kcal/mol for PI3K, exceeding DOX by over 20%.
Compound 09 exhibited a binding free energy of ΔG = −132.37 kcal/mol for ERα with improved interaction contributions.
Several derivatives met favorable drug-like characteristics, though some showed predicted low gastrointestinal absorption.

Abstract

Breast cancer continues to represent a critical global health concern, underscoring the need for more effective and less toxic therapeutic strategies. This study explores the potential of resveratrol and quercetin derivatives as anti-breast cancer agents using an integrated in silico approach. A combination of molecular docking, ADMET prediction, molecular dynamics (MD) simulations, and Prime MM-GBSA analysis was employed to comprehensively assess their biological potential. Twenty-five derivatives were evaluated against four clinically relevant protein targets: Aromatase (3HB5), PI3K (5NWH), ERα (6M7X), and Topoisomerase II (7RRF). Among the screened compounds, derivatives 09 and 22 demonstrated consistently strong binding across multiple targets, outperforming the reference drug doxorubicin (DOX), with docking scores ranging between −8.5 and − 11.2 kcal/mol. Pharmacokinetic profiling indicated favourable drug-like characteristics for several compounds, including appropriate lipophilicity and acceptable drug-likeness properties, although some glycosylated derivatives demonstrated low predicted gastrointestinal absorption due to their higher molecular weight and polarity, appropriate lipophilicity (LogP <5), and adherence to Lipinski's criteria, alongside low predicted toxicity risks. Dynamic behaviour of the ligand–protein complexes was further examined through 300 ns MD simulations, which confirmed stable interactions, as reflected by RMSD values below 3 Å and limited residue fluctuations within the binding sites. Binding free energy calculations highlighted the superior affinity of compound 22 toward PI3K (ΔG = −123.76 kcal/mol), exceeding that of DOX by over 20%, largely due to enhanced electrostatic and hydrophobic interactions. Likewise, compound 09 exhibited strong binding to ERα (ΔG = −132.37 kcal/mol), with improved van der Waals and lipophilic contributions relative to the reference compound. Overall, the results suggest that selected resveratrol and quercetin derivatives, particularly compounds 09 and 22, represent promising computationally predicted lead structures for further breast cancer research and experimental validation. Experimental validation is warranted to confirm their efficacy and potential for clinical translation.

Read Full Paperexternally

Mark Helpful

Bookmark

Relay

View Full Paper