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

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.