Cytotoxicity effect, network pharmacology, molecular docking, and molecular dynamics simulation of new mono-chalcone compounds for breast cancer

Abstract

Abstract Chalcones are flavonoids' derivatives and have a wide range of biological functions. Chalcones' anticancer efficacy arises from their capacity to operate on several targets. Hence, the purpose of this study was to examine cytotoxicity, network pharmacology, molecular docking, and molecular dynamics (MD) simulations of newly synthesized mono-chalcone compounds related to breast cancer. To achieve this objective, the cytotoxicity of mono-chalcone compounds in relation to breast cancer cells, specifically MCF-7 and MDA-MB-231, was investigated. The results demonstrated that the compounds were significantly suppressed in both breast cancer cells. Subsequently, the compounds were subjected to a network pharmacology analysis. The findings showed that both the compounds and the breast cancer target network shared 160 protein targets. In addition, it was discovered that most of the targeted proteins are involved in cancer pathways. The apoptosis proteins known as BCL2, MDM2, and CASP3 were the enriched genes identified in this analysis. Molecular docking analysis showed that the compounds had high binding affinities for their respective protein receptors. Therefore, the protein-ligand conformations were subjected to a 100 ns MD simulation at 310 K. Comparatively to the reference proteins, the protein-ligand conformation complexes exhibited greater stability, compactness, and negligible structural changes. The results indicate that both mono-chalcone compounds are of great significance and shed light on the molecular interactions between these compounds and proteins involved in the apoptosis breast cancer pathway.