Design, synthesis, biological evaluation of benzoyl amide derivatives containing nitrogen heterocyclic ring as potential VEGFR-2 inhibitors

Abstract For the purpose of synthesizing drug candidates with desirable bioactivity, a class of benzoyl amide containing nitrogen heterocyclic ring derivatives targeting VEGFR-2 was designed and screened out using Discovery Studio. Eighteen target compounds were synthesized and then selected by some biological trials sequentially including inhibition of VEGFR-2, anti-proliferation in vitro , flow cytometry. Among them, compound 8h showed the best inhibitory activity (IC 50 = 0.34 ±0.02 μ M against VEGFR-2, IC 50 = 1.08 ± 0.06 μ M and 2.44 ± 0.15 μ M against MCF-7 and HepG-2, respectively, which were at the same inhibitory level with the commercially antitumor drug: vandetanib). In addition, flow cytometry demonstrated that compound 8h induced MCF-7 cell apoptosis through a cell membrane-mediated pathway. This research highlights the therapeutic potential of novel VEGFR-2 inhibitors in treating cancers and provides a promising strategy for drug discovery.