Phytochemicals from Daucus carota have therapeutic potential against Triple-Negative Breast Cancer PDK1 and PLK1.

Triple-negative breast cancer (TNBC) is a deadly form of breast cancer that lacks estrogen, progesterone, and HER2 receptors. The development of drugs for TNBC has been challenging due to the lack of specific therapeutic targets. However, recent studies have shown that targeting the ATP active of the PDK-1 and PLK-1 proteins could be potential drug targets for TNBC treatment. New medications for TNBC have considerable adverse effects, highlighting the need for more targeted and effective therapies. In this study, we employed various computational approaches, including molecular docking, molecular dynamics (MD) simulations, pharmacokinetic studies, binding free energy calculations, principal component analysis (PCA), and alanine scanning analysis, to identify bioactive compounds from Daucus carota-extracted natural compounds that can bind to these ATP-binding sites and inhibit the activity of PDK1 and PLK1. Our study revealed that eight compounds showed reasonably good docking scores, binding free energies, and ADMET properties against the PDK1 and PLK1 enzymes. Astragalin and scolimoside showed substantial binding affinity and persistent interactions in the pocket region of the two proteins. Further MD simulation studies for 150 ns also suggested that the compounds were stably bound in the active site with very minor fluctuations. We believe that the identified hits for PDK1 and PLK1 from Daucus carota will be effective against TNBC in performing the biological assays.