Unravelling the potential of selected phenolics against breast cancer targets: Molecular docking and molecular dynamics investigations

Abstract

The multi-faceted problems of drug resistance, non-specificity, and toxicity have been identified as the major factors responsible for the dwindling efficacy of the current treatment options for breast cancer, including chemotherapy. Hence, the need for new compounds with enhanced specificity and improved efficacy for breast cancer treatment. Thus, in this study, thirty-four natural phenolic compounds were virtually screened against targeted apoptotic proteins, using molecular docking, as well as the ADMET and drug-likeness evaluation; then validated via molecular dynamic simulation at 310 K for 100 ns. After the docking analysis, seven compounds including amentoflavone, bicoumarin, didymin sesamolin, tanshinone and theaflavin were selected due to their notable binding affinities to the different oncogenic targets. Further results showed that tanshinone, bicoumarin, and sesamolin possess the highest potential for oral drug development, as they showed no violations of the Lipinski's rule of 5. Molecular dynamic simulation of the final three phenolics with the apoptotic proteins showed that the obtained protein-ligand conformations were stable and compact. Compared to the free protein, the phenolic-target complex also showed minimal alterations while competing favourably with the standard, tamoxifen. These findings thus highlight the three compounds as hits and potential leads in the therapeutic battle against breast cancer.