Investigating the potential of mono-chalcone compounds in targeting breast cancer receptors through network pharmacology, molecular docking, molecular dynamics simulation, antiproliferative effects, and gene expressions

The study aims to investigate various aspects of synthesized mono-chalcone compounds 5 and 8 concerning breast cancer, including network pharmacology, molecular docking, molecular dynamics (MD) simulations, antiproliferative effects, and gene expressions. Initially, the compounds underwent a network pharmacology analysis targeting breast cancer-related targets, with MalaCards, SwissTargetPrediction, and PharmMapper identifying 70 breast cancer target receptors. Subsequently, protein-protein interaction (PPI) network analysis revealed two distinct target gene clusters. Survival analysis identified seven significant target genes following Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) evaluation. Molecular docking and MD simulations were conducted on these seven target genes (AKT2, BRAF, ESR1, FGFR1, IGF1, IGF1R, and KIT), revealing that compound 8 exhibited the highest binding affinities, as well as better stability and compactness when interacting with the targeted proteins. Next, the compounds underwent cell viability assay and gene expression analysis to validate the in silico findings. Both compounds demonstrated the ability to suppress breast cancer proliferation, with compound 8 showing increased selectivity in targeting breast cancer cells while causing minimal harm to normal breast cells. The suppression of breast cancer cell proliferation was attributed to decreased expression levels of AKT2, BRAF, FGFR1, IGF1, IGF1R, KIT, and ESR1. Hence, the results provide insights into the molecular interaction responsible for the anti-breast cancer capabilities of mono-chalcone compounds.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-024-03991-y.