A reverse docking approach to explore the anticancer potency of natural compounds by interfering metastasis and angiogenesis

Abstract

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:

• Reverse docking
• MD simulation
• phytocompounds
• angiogenesis
• metastasis

Acknowledgments

All the authors are grateful to Kazi Md. Ali Zinnah for his support and supervision throughout the research.

Authors’ contributions

Anindita Ash Prome: conceptualization, formal analysis, methodology, project administration, visualization, writing–original draft, writing–review & editing; Tanjin Barketullah Robin: conceptualization, formal analysis, methodology, project administration, visualization, writing–original draft, writing–review & editing; Nadim Ahmed: conceptualization, formal analysis, writing–original draft, writing–review & editing; Nurul Amin Rani: conceptualization, formal analysis, writing–original draft, writing–review & editing; Iqrar Ahmad: MD simulation, writing–original draft, writing–review & editing; Harun Patel: MD simulation, writing–original draft, writing–review & editing; Md Nazmul Islam Bappy: conceptualization, methodology, formal analysis, writing–original draft, writing–review & editing; Kazi Md. Ali Zinnah: supervision, writing–review & editing.

Data availability statement

The corresponding author can provide the data that were used to support the study’s conclusions upon request.

Disclosure statement

In this work, the authors report no conflicts of interest.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.