Design and synthesis of sorafenib-inspired benzofuran hybrids as VEGFR-2 inhibitors: antiproliferative evaluation, mechanistic insights, and docking studies in hepatocellular carcinoma

= 0.069 μM). In HepG-2 cells, 7g induced G0/G1 arrest and apoptosis, upregulating Bax, caspase-8 and -9, and downregulating Bcl-2. Molecular docking confirmed the strong binding affinity of 7g within the VEGFR-2 active site through key interactions with Glu885, Asp1046, and Cys1045, mirroring sorafenib. A 100 ns molecular dynamics simulation further demonstrated that compound 7g retains a highly stable binding mode within VEGFR-2, supported by low RMSD fluctuations and persistent key hydrogen-bond and hydrophobic interactions. These findings nominate 7g as a promising VEGFR-2-targeted lead for HCC upon further optimization.