Angiogenesis, which results in the formation of new blood and lymph vessels, is required to serve metastatic cancer progression. Cancer medications may target these two interconnected pathways. Phytocompounds have emerged as promising options for treating cancer. In this study, we used a reverse docking strategy to find new candidate molecules for cancer treatment that target both pathways. Following a literature study, the important cancer-causing proteins vascular endothelial growth factor D (VEGF-D) and basic fibroblast growth factor (bFGF) for angiogenesis and matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) for the metastatic pathway were targeted. Protein Data Bank was used to retrieve the structures of chosen proteins. 22 significant plant metabolites were identified as having anticancer activity. To determine the important protein binding residues, active site prediction was used. Using Lenvatinib and Withaferin A as reference ligands, the binding affinity of certain proteins for plant metabolites was determined by docking analysis. Homoharringtonine and viniferin, both have higher binding affinities when compared to reference ligands, with docking scores of -180.96 and -180.36 against the protein MMP-9, respectively. Moreover, Viniferin showed the highest binding affinity with both MMP-9 and MMP-2 proteins, which were then subjected to a 100-ns molecular dynamic simulation. where they were found to be significantly stable. In pharmacoinformatics investigations, the majority of our compounds were found to be non-toxic for the host. In this study, we suggested natural substances as cutting-edge anticancer treatments that target both angiogenesis and metastasis, which may aid in accelerating drug development and identifying viable therapeutic candidates.Communicated by Ramaswamy H. Sarma.
Keywords: MD simulation; Reverse docking; angiogenesis; metastasis; phytocompounds.