Comparative study of isoflavone, quinoxaline and oxindole families of anti-angiogenic agents.
Comparative study of isoflavone, quinoxaline and oxindole families of anti-angiogenic agents.
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异黄酮、喹喔啉和羟吲哚家族抗血管生成剂的比较研究。
DOI：
10.1023/a:1021528628524
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发表时间：
2002
期刊：
影响因子：
9.8
通讯作者：
Moody,ChristopherJ
中科院分区：
文献类型：
--
作者：
Whatmore,JacquelineL;Swann,Elizabeth;Barraja,Paola;Newsome,JefferyJ;Bunderson,Melisa;Beall,HowardD;Tooke,JohnE;Moody,ChristopherJ
进行了一项旨在比较多种已知抗血管生成剂及其一些新衍生物对VEGF诱导的血管生成的作用的研究。因此，选择了鹰嘴豆芽素A1、吲哚美辛2、3-芳基喹喔啉SU 1433及其衍生物3 -6、苯甲酸衍生物7、羟吲哚SU 54168和SU 666811及其简单的N-苄基衍生物9、10和12进行研究。使用anin vitroassay的化合物进行了评价，其抑制VEGF诱导的血管生成的HUVEC的能力，和代表性的化合物的细胞毒性也进行了研究，在肿瘤细胞系中使用24小时的曝光。结果表明SU化合物SU 1433、SU 5416和SU 6668是比吲哚美辛或天然存在的鹰嘴豆芽素A更有效的VEGF诱导的血管生成抑制剂，这可能是因为它们抑制VEGF受体信号传导。阻断SU 1433的酚羟基之一降低了抗血管生成活性，阻断SU 5416和SU 6668的NH基团也是如此。细胞毒性研究表明，在抗血管生成浓度下，所检测的化合物均未表现出细胞毒性。
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 A1, indomethacin2, the 3-arylquinoxaline SU1433 and its derivatives3–6, the benzoic acid derivative7, the oxindoles SU54168and SU666811, together with their simpleN-benzyl derivatives9,10, and12were selected for study. Using anin vitroassay 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.