Novel VEGFR-2 inhibitors with an N-acylhydrazone scaffold.

Abstract

Vascular endothelial growth factor receptor 2 (VEGFR-2) is a tyrosine kinase that mediates a large number of cell responses associated with angiogenesis. The control of the angiogenic pathway in tumorigenesis by the inhibition of VEGFR-2 is considered a promising therapeutic strategy for the prevention and control of solid tumor growth. In this study, the design, synthesis, and biological evaluation of a novel series of VEGFR-2 inhibitors with an N-acylhydrazone (NAH) scaffold (9a-h) are reported. The molecular design is validated by docking studies and by in vitro inhibitory activity assays. Compounds 9b, 9c, 9d, and 9f effectively inhibited neovascularization induced by VEGF in the chorioallantoic membrane assay. Thus, these NAH derivatives are promising antiangiogenic prototypes.

• Authors: Fernanda P Pauli, Juliana R Martins, Thaysa Paschoalin, Marisa Ionta, Maria Leticia C Barbosa, Eliezer J Barreiro
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 353 Issue 11 Pg. e2000130 (Nov 2020) ISSN: 1521-4184 [Electronic] Germany
• PMID: 32667721 (Publication Type: Journal Article)
• Copyright: © 2020 Deutsche Pharmazeutische Gesellschaft.

Chemical References

• Angiogenesis Inhibitors
• Hydrazones
• Protein Kinase Inhibitors
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Angiogenesis Inhibitors (chemical synthesis, pharmacology)
• Animals
• Chick Embryo
• Chorioallantoic Membrane (blood supply)
• Drug Design
• Hydrazones (chemical synthesis, pharmacology)
• Molecular Docking Simulation
• Molecular Structure
• Molecular Targeted Therapy
• Neovascularization, Physiologic (drug effects)
• Protein Kinase Inhibitors (chemical synthesis, pharmacology)
• Structure-Activity Relationship
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors, metabolism)