1. Design, synthesis, and biological evaluation of tetrahydroisoquinoline-based diaryl urea derivatives for suppressing VEGFR-2 signaling.
- Author
-
Huang Y, Zhang Y, Li J, Ma X, Hu M, Yang Y, and Gao S
- Subjects
- Human Umbilical Vein Endothelial Cells metabolism, Humans, Molecular Docking Simulation, Structure-Activity Relationship, Urea chemistry, Vascular Endothelial Growth Factor Receptor-2 metabolism, Cell Proliferation, Drug Design, Human Umbilical Vein Endothelial Cells drug effects, Neovascularization, Physiologic drug effects, Tetrahydroisoquinolines chemistry, Urea pharmacology, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors
- 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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