Comparative study of isoflavone, quinoxaline and oxindole families of anti-angiogenic agents

Angiogenesis. 2002;5(1-2):45-51. doi: 10.1023/a:1021528628524.

Abstract

A study designed to compare the effects on VEGF-induced angiogenesis of a number of known anti-angiogenic agents together with some novel derivatives thereof was undertaken. Thus the isoflavone biochanin A 1[structure: see text], indomethacin 2[structure: see text], the 3-arylquinoxaline SU1433 and its derivatives 3-6[structure: see text], the benzoic acid derivative 7[structure: see text], the oxindoles SU5416 8[structure: see text] and SU6668 11[structure: see text], together with their simple N-benzyl derivatives 9, 10, and 12[structure: see text] were selected for study. Using an in vitro assay the compounds were evaluated for their ability to inhibit VEGF-induced angiogenesis in HUVECs, and the cytotoxicity of representative compounds was also studied in tumour cell lines using 24-h exposure. The results indicate that the SU compounds, SU1433, SU 5416 and SU6668, are more potent inhibitors of VEGF-induced angiogenesis than indomethacin or the naturally occurring biochanin A, presumably because they inhibit VEGF receptor signalling. Blocking one of the phenolic OH groups of SU1433 reduced anti-angiogenic activity, as did blocking the NH groups of SU5416 and SU6668. Cytotoxicity studies indicate that none of the compounds examined exhibited cytotoxicity at anti-angiogenic concentrations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Endothelium, Vascular / drug effects
  • Humans
  • Indoles / pharmacology*
  • Isoflavones / pharmacology*
  • Neoplasms / blood supply
  • Neoplasms / drug therapy
  • Neovascularization, Pathologic / drug therapy*
  • Oxindoles
  • Propionates
  • Pyrroles / pharmacology*
  • Quinoxalines / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • Indoles
  • Isoflavones
  • Oxindoles
  • Propionates
  • Pyrroles
  • Quinoxalines
  • Semaxinib
  • orantinib