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

Autor: Pauli FP; Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, CCS, Rio de Janeiro, RJ, Brazil.; Graduate Program in Chemistry (PGQu), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Martins JR; Department of Drugs and Medicines, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Brazil., Paschoalin T; Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil., Ionta M; Department of Drugs and Medicines, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Brazil., Barbosa MLC; Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, CCS, Rio de Janeiro, RJ, Brazil.; Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Barreiro EJ; Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro, CCS, Rio de Janeiro, RJ, Brazil.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2020 Nov; Vol. 353 (11), pp. e2000130. Date of Electronic Publication: 2020 Jul 15.
DOI: 10.1002/ardp.202000130
Abstrakt: 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.
(© 2020 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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