1. Design, synthesis, and biological evaluation of tetrahydroisoquinoline-based diaryl urea derivatives for suppressing VEGFR-2 signaling
- Author
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Xiaodong Ma, Yang Zhang, Yuanzheng Huang, Gao Sufan, Jiaming Li, Mengqi Hu, and Yu Yang
- Subjects
0301 basic medicine ,Cancer Research ,Angiogenesis ,Neovascularization, Physiologic ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tetrahydroisoquinolines ,Human Umbilical Vein Endothelial Cells ,Humans ,Urea ,Structure–activity relationship ,Pharmacology (medical) ,Cell Proliferation ,Pharmacology ,Tube formation ,Tetrahydroisoquinoline ,Cell growth ,Vascular Endothelial Growth Factor Receptor-2 ,Molecular Docking Simulation ,030104 developmental biology ,Oncology ,chemistry ,Biochemistry ,Cell culture ,Drug Design ,030220 oncology & carcinogenesis ,Phosphorylation ,Human umbilical vein endothelial cell - Abstract
A novel structural series of tetrahydroisoquinoline-based compounds that incorporate the diaryl urea moiety was designed, synthesized, and biologically evaluated as suppressors of VEFGR-2 signaling. As a consequence, compounds 9k and 9s exhibited comparable or superior cytotoxic activity to that of gefitinib against the tested three cell lines, including A549, MCF-7, and PC-3. Importantly, both of them downregulated the expression of VEGFR-2, and inhibited VEGFR-2 phosphorylation at the concentration of 0.5 or 1.0 μmol/l. Besides, they suppressed human umbilical vein endothelial cell tube formation at the concentration of 4.0 μmol/l. Considering their capability of down-regulating VEGFR-2 expression and inhibiting VEGFR-2 phosphorylation, 9k and 9s may serve as suppressors of angiogenesis for further investigation.
- Published
- 2019
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