In-silico based identification of phytochemicals from Houttuynia cordata Thunb. as potential inhibitors for overexpressed HER2 and VEGFR2 cancer genes

Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (VEGFR2) - a tyrosine kinase receptors play a key role in breast and stomach cancers. The overexpression of HER2 and VEGFR2 genes increases the number of HER2 and VEGFR2 in the cell which initiates breast and stomach cancer respectively. The phytochemicals from traditional medicinal herb Houttuynia cordata Thunb. are reported to possess anti-inflammatory and anti-cancer potential. However, isolation of phytochemicals from this herb is fraught with uncertainly and time-consuming. Here, a molecular docking approach provides probable binding affinities between the receptors and phytochemicals (ligands) which initiate the first step of anticancer drug discovery and development. In the present study, In-silico docking approaches were used to identify the top-hit phytochemicals from H. cordata as potential inhibitors for overexpressed HER2 (breast) and VEGFR2 (stomach) cancer genes. A total of 100 biologically active phytochemicals from H. cordata were screened and docked against the ligand-binding pocket of HER2 and VEGFR2 kinase domains. Docking results revealed only a few phytochemicals (molecules) which appropriately fit into the ligand-binding pocket with higher binding affinity than the natural ATP ligand. A competitive docking was used to ascertain the top-hit phytochemicals that bind perfectly to the ATP ligand-binding pocket. Among the top-hit phytochemicals docked from H. cordata, the beta-sitosterol and Quercetin showed highest binding affinity towards HER2 and VEGFR2 receptors using both hydrogen and hydrophobic interactions. This study confirmed beta-sitosterol and Quercetin as potential drug candidates against breast and stomach cancer. Communicated by Ramaswamy H. Sarma

Automated summary

In this study, a molecular docking approach was used to screen potential inhibitors from Houttuynia cordata for overexpressed HER2 and VEGFR2 cancer genes. Among the top-hit phytochemicals, beta-sitosterol and Quercetin showed the highest binding affinity towards HER2 and VEGFR2 receptors, indicating their potential as drug candidates for breast and stomach cancer.