Natural Products as Chemopreventive Agents by Potential Inhibition of the Kinase Domain in ErbB Receptors

Molecules. 2017 Feb 17;22(2):308. doi: 10.3390/molecules22020308.


Small molecules found in natural products provide therapeutic benefits due to their pharmacological or biological activity, which may increase or decrease the expression of human epidermal growth factor receptor (HER), a promising target in the modification of signaling cascades involved in excessive cellular growth. In this study, in silico molecular protein-ligand docking protocols were performed with AutoDock Vina in order to evaluate the interaction of 800 natural compounds (NPs) from the NatProd Collection (, with four human HER family members: HER1 (PDB: 2ITW), HER2 (PDB: 3PP0), HER3 (PDB: 3LMG) and HER4 (PDB: 2R4B). The best binding affinity values (kcal/mol) for docking pairs were obtained for HER1-podototarin (-10.7), HER2-hecogenin acetate (-11.2), HER3-hesperidin (-11.5) and HER4-theaflavin (-10.7). The reliability of the theoretical calculations was evaluated employing published data on HER inhibition correlated with in silico binding calculations. IC50 values followed a significant linear relationship with the theoretical binding Affinity data for HER1 (R = 0.656, p < 0.0001) and HER2 (R = 0.543, p < 0.0001), but not for HER4 (R = 0.364, p > 0.05). In short, this methodology allowed the identification of several NPs as HER inhibitors, being useful in the discovery and design of more potent and selective anticancer drugs.

Keywords: AutoDock Vina; HER receptors; molecular docking; natural compounds.

MeSH terms

  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biological Products / chemistry
  • Biological Products / pharmacology*
  • Chemoprevention
  • Computer Simulation
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / chemistry
  • Humans
  • Molecular Conformation
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Protein Interaction Domains and Motifs / drug effects*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Quantitative Structure-Activity Relationship


  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Biological Products
  • Protein Kinase Inhibitors
  • ErbB Receptors