Lagerstroemin from Lagerstroemia speciosa as Antibreast Cancer Candidate Targeting AURKA, EGFR and SRC Protein: A Comprehensive Computational Study

Abstract

Breast cancer is a type of cancer that has a high rate of diagnosis and mortality in the world. Lagerestroemia speciosa is a herb that has anticancer activity. This study aims to analyze the compounds in L. speciosa that most act as anticancer of the breast. The compounds in L. speciosa were selected based on drug-likeness, physicochemical properties, ability to penetrate the lipid bilayer and toxicity. The Lagerstroemin target related to Lagestroemin breast cancer was predicted using DisGeNET, SWISS Target Prediction and cBioportal. Molecular docking between Lagerstroemin and AURKA, EGFR and SRC was performed using AutoDock Vina. The interaction stability of each complex was analyzed by molecular dynamic simulation using YASARA with parameters of RMSD protein, RMSD ligand, number of hydrogen bonds and molecular dynamic binding energy. Of the 22 compounds, Quercetin, Caffeic acid, Lagerstroemin and Dypirone were predicted to have good ADME properties and can easily penetrate lipid membranes. Therefore, Quercetin, Caffeic acid and Lagerstroemin were predicted to have anti-breast cancer bioactivity. Of the 3 compounds, Lagerstroemin had the lowest toxicity. Lagerstroemin was predicted to interact with breast cancer-related proteins AURKA, EGFR and SRC. Molecular docking and dynamics showed that Lagerestroemin interacted stably at the ATP binding site of the 3 proteins, so it was very potential as an inhibitor of these 3 proteins. Therefore, Lagerstroemin was predicted to be the compound in L. speciosa with the most potential breast anticancer agent by targeting AURKA, EGFR and SRC. HIGHLIGHTS Quercetin, Caffeic acid and Lagerstroemin from Lagerstroemia speciosa show promising anticancer properties for breast cancer treatment. Lagerstroemin stands out with low toxicity and potent anticancer activity, suggesting its safety and effectiveness as a therapeutic agent. Lagerstroemin interacts stably with breast cancer-related proteins AURKA, EGFR and SRC, indicating its potential as a powerful inhibitor targeting key pathways in breast cancer. GRAPHICAL ABSTRACT