Design, synthesis, biological evaluation of benzoyl amide derivatives containing nitrogen heterocyclic ring as potential VEGFR-2 inhibitors
- Bioorg Med Chem. 2019 Sep 1;27(17):3813-3824. doi: 10.1016/j.bmc.2019.07.007.
- 1. Zhengzhou Children's Hospital, ZZ 450018, China; State Key Laboratory of Pharmaceutical Biotechnology, NJ 210023, China.
- 2. Zhengzhou Children's Hospital, ZZ 450018, China; State Key Laboratory of Pharmaceutical Biotechnology, NJ 210023, China. Electronic address: [email protected].
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 (IC50 = 0.34 ± 0.02 μM against VEGFR-2, IC50 = 1.08 ± 0.06 μM and 2.44 ± 0.15 μM 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.