Abstract
The coumarin nucleus is a simple privileged scaffold distributed in many plants. It has recently gained attention for its diverse biological activities and interactions with enzymes and receptors. The vascular endothelial growth factor receptor-2 (VEGFR-2), a receptor tyrosine kinase, is a crucial cancer target as it is involved in angiogenesis. This study employs virtual screening, molecular docking, and molecular simulation studies to identify potential coumarin candidates against VEGFR-2 from the COCONUT database. After thorough docking studies, CNP0056360, CNP0340213, and CNP0366287 were identified as final hits. Molecular dynamics simulation studies revealed strong stability and better binding energies for CNP0056360 and CNP0340213, outperforming lenvatinib; CNP0366287 showed comparable behaviour. The identified coumarins exhibited good in-silico pharmacokinetics and demonstrated low toxicity.
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The files associated with the research could be freely assessed on “https://zenodo.org/records/10646050”.
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Acknowledgements
The authors extend their gratitude toward Professor David A. Case, Department of Chemistry & Chemical Biology, Rutgers University, New Jersey, USA, for granting a licence for Amber 20. NT and NB are also thankful to IIT (BHU) and Ministry of Education (MoE), New Delhi for providing teaching assistantship.
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This work was partially supported by the SERB-CRG Grant (Grant No. CRG/2022/001637).
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Nancy Tripathi: Conceived, designed, and performed the experiments; Analyzed the data; Writing original draft. Nivedita Bhardwaj: Prepared figures and tables; Paper formatting. Bikarma Singh: Conceived and designed the experiments. Shreyans K. Jain: Conceived and designed the experiments; Supervision; Final paper review and formatting.
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Tripathi, N., Bhardwaj, N., Singh, B. et al. In-silico identification of Coumarin-based natural compounds as potential VEGFR-2 inhibitors. Chem. Pap. 78, 4347–4360 (2024). https://doi.org/10.1007/s11696-024-03395-5
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DOI: https://doi.org/10.1007/s11696-024-03395-5