Novel VEGFR‐2 inhibitors with an N‐acylhydrazone scaffold. Issue 11 (15th July 2020)

• Record Type: Journal Article
• Authors: Pauli, Fernanda P.; Martins, Juliana R.; Paschoalin, Thaysa; Ionta, Marisa; Barbosa, Maria Leticia C.; Barreiro, Eliezer J.
• Is Part Of: Archiv der Pharmazie. Volume 353:Issue 11(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-07-15
• Subjects: angiogenesis inhibitor -- kinase inhibitor -- LASSBio‐2027 -- N‐acylhydrazone -- VEGFR‐2; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202000130
• Languages: English
• ISSNs: 0365-6233

Abstract

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. Abstract : VEGFR‐2 is a tyrosine kinase that mediates cell responses associated with angiogenesis, and its modulation is considered a promising strategy in the prevention and control of solid tumor growth. The design, synthesis, and enzyme inhibitory and antiangiogenic activities of a novel series of VEGFR‐2 inhibitors with an N ‐acylhydrazone scaffold are reported in this study. Compounds 9b –f effectively inhibited neovascularization induced by VEGF.