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, indomethacin 2, the 3-arylquinoxaline SU1433 and its derivatives 3–6, the benzoic acid derivative 7, the oxindoles SU5416 8 and SU6668 11, together with their simple N-benzyl derivatives 9, 10, and 12 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, SU5416 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.
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Whatmore, J.L., Swann, E., Barraja, P. et al. Comparative study of isoflavone, quinoxaline and oxindole families of anti-angiogenic agents. Angiogenesis 5, 45–51 (2002). https://doi.org/10.1023/A:1021528628524
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DOI: https://doi.org/10.1023/A:1021528628524