Development of Novel Molecular Drug Candidates Using Molecular Docking Techniques in theContext of Breast Cancer

The most common cancer among women in the world is breast cancer. In Iran, the incidence of breast cancer is increasingly rising and it is among the five most common cancers. Many of natural compounds have high chemo-preventive potential which could be sought to be used in drug discovery. Many studies have shown the incidence rate of cancers such as breast, colon, and prostate are decreased in communities if they would consume cruciferous vegetable. Sulforaphane is one of the isothiocyanates-derived compounds from cruciferous vegetables which bears up such characteristic. Sulforaphane is an electrophile compound which has high tendency to react with sulfhydryl. The target of this compound is sought to be residues of cysteine of many proteins which control the regulatory process of cancer in the cells. The mechanism of sulforaphane is to modify cysteine residues in Keap1 (kelch-like ECH-associated protein 1) in such way to stabilize Nrf2 (Nuclear factor (erythroid-derived 2)-like 2). This stabilization would culminate in activating antioxidant response element (ARE) of phase 2 enzymes. In this study, the structure of protein of interest, Keap1, and highly similar analogues (90%) from PDB and Pubchem websites were respectively downloaded. Then molecular simulation andcalculation of docking energy (ligand-protein) by Autodock 4.2 was performed to reach sulforaphanesimilar compounds. In this way, a figurative library with around 300 molecules was generated. Finally we identified CID:52666086, CID:5076735 and CID:13352380 with the lowest docking energy. The aforementioned molecules could be assumed as breast cancer drug candidates.

Keywords:

Cancer , Sulforaphane , Drug Design , Molecular Docking