New chromene derivatives as promising VEGFR-2 inhibitors: combined experimental, DFT, and molecular dynamics approaches

AIMS: This study aimed to design and synthesize a novel series of chromene derivatives as potential vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors with anticancer activity. MATERIALS AND METHODS: cytotoxicity against cancer cell lines (MCF-7, MDA-MB-231, HepG-2, and HCT-116) and normal cells (WI-38 and WISH). VEGFR-2 inhibitory activity was determined. Mechanistic studies included wound healing assays, cell cycle analysis, apoptosis evaluation, and expression analysis of apoptosis-related markers. Molecular docking and 200 ns molecular dynamics simulations with MM-GBSA, Protein-Ligand Interaction Fingerprinting (Pro-LIF), Principal Component Analysis (PCA), and Free Energy Landscape (FEL) analyses were performed to assess ligand-protein interactions and complex stability. RESULTS: investigation.