In-silico identification of Coumarin-based natural compounds as potential VEGFR-2 inhibitors

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. Graphical Abstract: (Figure presented.). © The Author(s), under exclusive licence to the Institute of Chemistry, Slovak Academy of Sciences 2024.