2. Academic Validation
  3. Discovery of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives as novel VEGFR-2 kinase inhibitors

Discovery of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives as novel VEGFR-2 kinase inhibitors

  • Eur J Med Chem. 2014 Sep 12:84:698-707. doi: 10.1016/j.ejmech.2014.07.071.
Lei Shi 1,  Ting-Ting Wu 2,  Zhi Wang 2,  Jia-Yu Xue 3,  Yun-Gen Xu 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: shilei@cpu.edu.cn.
  • 2 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China.
  • 3 Jiangsu Provincial Key Laboratory for Plant Ex Situ Conservation, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, PR China.
  • 4 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: xyg@cpu.edu.cn.
PMID: 25064347 DOI: 10.1016/j.ejmech.2014.07.071
Abstract

Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. In this work, a series of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinolin-4-amine derivatives were designed and identified as potent inhibitors of VEGFR-2 (VEGFR2/KDR/Flk-1) kinase. These compounds with quinoline scaffold and benzimidazole moiety were synthesized and their biological activities against VEGFR-2 and two human Cancer cell lines were evaluated. Among them, compound 7s exhibited the most potent inhibitory activity against VEGFR-2 with IC50 of 0.03 μM and it also showed the highest Anticancer activity against the tested Cancer cell lines with IC50 of 1.2 μM against MCF-7 and 13.3 μM against Hep-G2. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of VEGFR-2, which demonstrates that compound 7s is a potential agent for Cancer therapy deserving further researching.

Keywords

Antitumor; Benzimidazole; Quinolin; VEGFR-2 kinase inhibitor.

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