In Silico Identification of 9‐Amino Camptothecin as a Dual Inhibitor of VEGF‐A and VEGF‐B in N1–N8 Breast Cancer

Angiogenesis is the process of the formation of blood vessels from pre-existing ones, which is required for the supply of sufficient oxygen and nutrition for tumor growth. Components of angiogenesis, such as vascular endothelial growth factors, can specifically bind to vascular endothelial growth factor receptor-1 (VEGFR-1), playing an essential role in the lymphangiogenesis of breast cancer. Among 20 different compounds, three ligands showed interaction with the protein molecule such as 9-amino camptothecin, 10-hydroxy camptothecin, and 9-methoxy camptothecin, obtained from Mappia foetida. This work emphasizes the role of 9-amino-camptothecin as an antagonist for both VEGF-A and VEGF-B, which mediate aggressive breast cancer. VEGF-B can induce cell survival by binding through VEGFR-1 whereas in the case of VEGF-A, it can activate VEGFR-1 and VEGFR-2 is a prominent growth factor for both hemangiogenesis and lymphangiogenesis. For conducting molecular docking, identifying druglikeness and also determining active sites of the proteins and ligands, were observed in this insilico work. This work highlights the necessity of preserving M. foetida due to its camptothecin contents within the plant, along with its interaction in the presence of two proteins (VEGF-A and VEGF-B). These aspects are crucial for developing potential treatments for metastatic breast cancer. The core finding of this study is that 9-amino camptothecin can interact with VEGF-A and VEGF-B through hydrogen bonding. This interaction potentially establishes targets for VEGF-induced N1-N8 breast cancer.