2. Academic Validation
  3. Discovery of novel VEGFR-2 inhibitors embedding 6,7-dimethoxyquinazoline and diarylamide fragments

Discovery of novel VEGFR-2 inhibitors embedding 6,7-dimethoxyquinazoline and diarylamide fragments

  • Bioorg Med Chem Lett. 2021 Mar 15:36:127788. doi: 10.1016/j.bmcl.2021.127788.
Ru Wang 1,  Hu Liu 1,  Yuan-Yuan You 1,  Xin-Yu Wang 1,  Bing-Bing Lv 1,  Li-Qin Cao 1,  Jia-Yu Xue 2,  Yun-Gen Xu 3,  Lei Shi 4
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 2 Jiangsu Provincial Key Laboratory for Plant Ex Situ Conservation, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
  • 3 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xyg@cpu.edu.cn.
  • 4 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: shilei@cpu.edu.cn.
PMID: 33460739 DOI: 10.1016/j.bmcl.2021.127788
Abstract

VEGF/VEGFR-2 signaling plays a critical part in tumor angiogenesis. Inhibition of this pathway has been considered as a promising approach for Cancer treatment. In this work, a series of 6,7-dimethoxy-4-anilinoquinazoline derivatives bearing diarylamide moiety were designed, synthesized and evaluated as potent inhibitors of VEGFR-2 kinase. Their in vitro antiproliferation activities against two human Cancer cell lines Hep-G2 and MCF-7 have also been determined. Among them, compound 14b exhibited the most potent inhibitory activity against VEGFR-2 with IC50 value of 0.016 ± 0.002 µM and it showed the most potent antiproliferative effect against Hep-G2 and MCF-7 with IC50 values at low-micromolar range. Molecular docking studies revealed that these compounds represented by the most potent compound 14b could bind well to the ATP-binding site of VEGFR-2, which suggested that compound 14b could be a potential Anticancer agent targeting VEGFR-2.

Keywords

6,7-Dimethoxy-4-anilinoquinazoline; Cancer; Diarylamide; Inhibitor; VEGFR-2.

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