title: Natural Products as Chemopreventive Agents by Potential Inhibition of the Kinase Domain in ErbB Receptors.
abstract: 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 (http://www.msdiscovery.com/natprod.html), 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. IC50values 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.
authors.affiliation: Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena 130015, Colombia. moliveroa@unicartagena.edu.co.
authors.forename: Maria
authors.initials: M
authors.lastname: Olivero-Acosta
authors.affiliation: Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena 130015, Colombia. wmaldonador@unicartagena.edu.co.
authors.forename: Wilson
authors.initials: W
authors.lastname: Maldonado-Rojas
authors.affiliation: Environmental and Computational Chemistry Group, School of Pharmaceutical Sciences, Zaragocilla Campus, University of Cartagena, Cartagena 130015, Colombia. joliverov@unicartagena.edu.co.
authors.forename: Jesus
authors.initials: J
authors.lastname: Olivero-Verbel
mesh_terms: D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D018890:Chemoprevention; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D001688:Biological Products; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: AutoDock Vina; HER receptors; molecular docking; natural compounds