Screening and Docking Molecular Studies of Natural Products Targeting overexpressed Receptors HER-2 in Breast Cancer

Abstract

Breast cancer is the first cancer to affect a community. Because of its extremely high mitotic activity, breast cancer that tests positive for HER 2 is considered to have a poor prognosis. Due to the side effects of chemical drugs, patients are increasingly turning to natural medicine, such as phytotherapy and nutritherapy. The study uses a bioinformatics approach (molecular docking) to searchfor new, non-toxic anti-cancer inhibitors. The studyscreens 102 ligands from natural and dietary compounds that are likely to interact with the HER-2. The virtual screening results of the allow us to select the 23 best compounds which can be proposed as the most effective HER-2 inhibitors. Lycopene would be a very promising ligand which presents a DeltaG of -9.82 kcal/mol. Other promising ligands include beta-carotene (DeltaG of -8.58), P-cumaric acid kcal/mol (DeltaG of -8.57) and Curcumin (DeltaG of -8.46). Other compounds, luteolin, anacardium (Anacardic acid),and alpha-Tocopherol, were found to have the strongest inhibitory effects with DeltaG values of -7.92 kcal/mol, - 7.89 kcal/mol, and-7.85 kcal/mol, respectively. These compounds act directly on residues keys found in the hydrophobic pocket II (ATP binding site) and the hydrophobic region (the αC-β4 loop) of the EGFR domain. Pinoresinol, Kaempferol and Caffeic acid have DeltaGs of -7.48 Kcal/mol, -6.88 Kcal/mol and -6.34 kcal/mol, respectively. These three ligands are specific to the conserved regions of the HER-2 receptor and interact with the C-terminal, the C-lobe activation loop and the N-lobe P loop of the tyrosine kinase domain, respectively. Lapatinib (chemical compound) and quercetin (natural compound) have DeltaG of -7.58 kcal/mol and -7.28 kcal/mol, respectively, form a hydrogen bond with the same residue in the hydrophobic region. All the natural molecules seem very promising and, after in vitro/in vivo tests, could constitute good substitutes for the chemotherapies which are currently used to treat breast cancers as well as other cancers. Copy right