Screening in silico the human epidermal growth factor receptor-2 inhibitory effect of isoflavones by molecular docking method for their potential use in breast cancer

Abstract

Isoflavones are secondary phenolic metabolites found in most legumes. These compounds have important pharmacological significance such as anti-osteoporosis, anti-aging, and anti-cancer properties. Breast cancer is one of the most common cancers in women worldwide. Human epidermal growth factor receptor-2 (HER2) is an important target in breast cancer treatment. In this study, we evaluated the ability of sixty isoflavones compounds to inhibit the HER2 enzyme for their potential use in breast cancer treatments by the molecular docking method. Molecular docking was done by Autodock vina software. Lipinski 5 rule is used to compare compounds with drug-like and non-drug-like properties. Pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool. Our results showed that 35 compounds inhibited HER2 stronger than the positive control. Next, we analysed the drug-likeness according to Lipinski’s rule of five and predicted pharmacokinetic-toxicological parameters of these 35 compounds. We obtained two compounds, genistein and biochanin A, which could become promising drugs for breast cancer treatment. However, in vitro and in vivo studies on the inhibition of the HER2 enzyme need to be conducted.

Keywords

• biochanin A
• breast cancer
• genistein
• HER2
• isoflavone
• molecular docking