Discovery of novel picolinamide-based derivatives as novel VEGFR-2 kinase inhibitors: synthesis,in vitrobiological evaluation and molecular docking

Abstract

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive target for cancer therapy. In our effort, a novel series of picolinamide-based derivatives were designed and synthesized as potent and effective VEGFR-2 inhibitors. All the newly prepared compounds were evaluated <i>in vitro</i> for their antiproliferative activity against A549 and HepG2 cell lines. Among the new compounds, <b>8j</b> and <b>8l</b> exhibited better activity against both A549 and HepG2 cell lines. Molecular docking was performed to investigate the binding capacity and binding mode with VEGFR-2 (PDB code: ; 4ASD).