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

中文翻译：

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香豆素类天然化合物作为潜在 VEGFR-2 抑制剂的计算机鉴定

香豆素核是分布在许多植物中的简单的特权支架。它最近因其多样化的生物活性以及与酶和受体的相互作用而受到关注。血管内皮生长因子受体 2 (VEGFR-2) 是一种受体酪氨酸激酶，是重要的癌症靶标，因为它参与血管生成。本研究采用虚拟筛选、分子对接和分子模拟研究，从 COCONUT 数据库中识别出针对 VEGFR-2 的潜在香豆素候选物。经过彻底的对接研究，CNP0056360、CNP0340213 和 CNP0366287 被确定为最终命中。分子动力学模拟研究显示CNP0056360和CNP0340213具有很强的稳定性和更好的结合能，优于仑伐替尼； CNP0366287 显示出类似的行为。所鉴定的香豆素表现出良好的计算机药代动力学且毒性低。

图形概要