2. Academic Validation
  3. Discovery of arylamide-5-anilinoquinazoline-8-nitro derivatives as VEGFR-2 kinase inhibitors: Synthesis, in vitro biological evaluation and molecular docking

Discovery of arylamide-5-anilinoquinazoline-8-nitro derivatives as VEGFR-2 kinase inhibitors: Synthesis, in vitro biological evaluation and molecular docking

  • Bioorg Med Chem Lett. 2019 Dec 1;29(23):126711. doi: 10.1016/j.bmcl.2019.126711.
Yongqiang Zhao 1,  Feifei Liu 2,  Guojing He 1,  Ke Li 3,  Changcheng Zhu 4,  Wei Yu 5,  Conghai Zhang 1,  Mingjin Xie 1,  Jun Lin 6,  Jihong Zhang 7,  Yi Jin 8
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
  • 2 Laboratory of Molecular Genetics of Aging and Tumor, Medical School, Kunming University of Science and Technology, Kunming 650500, PR China.
  • 3 Biomedical Department, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, PR China. Electronic address: likelikelike@126.com.
  • 4 Institute of Drug Research and Development, Kunming Pharmaceutical Corporation, Kunming 650100, PR China.
  • 5 Pharmaceutical Department, Kunming General Hospital of Chengdu Military Command, Kunming 650118, PR China.
  • 6 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: linjun@ynu.edu.cn.
  • 7 Laboratory of Molecular Genetics of Aging and Tumor, Medical School, Kunming University of Science and Technology, Kunming 650500, PR China. Electronic address: zhjihong2000@126.com.
  • 8 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: jinyi@ynu.edu.cn.
PMID: 31668972 DOI: 10.1016/j.bmcl.2019.126711
Abstract

Herein, we embarked on a structural optimization campaign aiming at the discovery of novel Anticancer agents with our previously reported XL-6f as a lead compound. A library of 23 compounds has been synthesized based on the highly conserved active site of VEGFR-2. Several title compounds exhibited selective inhibitory activities against VEGFR-2, which also displayed selective anti-proliferation potency against HepG2 cell. All synthesized compounds were evaluated for anti-angiogenesis capability. Compound 7o showed the most potent anti-angiogenesis ability, the efficient cytotoxic activities (in vitro against HUVEC and HepG2 cell lines with IC50 values of 0.58 and 0.23 µM, respectively). The molecular docking analysis revealed 7o is a Type-II inhibitor of VEGFR-2 kinase. In general, these results indicated these arylamide-5-anilinoquinazoline-8-nitro derivatives are promising inhibitors of VEGFR-2 for the potential treatment of anti-angiogenesis.

Keywords

Antiangiogenesis; Anticancer agents; Quinazoline; VEGFR-2 kinase inhibitors.

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