Study of puupehenone and related compounds as inhibitors of angiogenesis
Study of puupehenone and related compounds as inhibitors of angiogenesis
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DOI：
10.1002/ijc.20068
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发表时间：
2004-05-20
影响因子：
6.4
通讯作者：
Quesada, AR
中科院分区：
文献类型：
--
作者：
Castro, ME;González-Iriarte, M;Quesada, AR
pupupehenone，一种由某些海绵产生的倍半萜，在一项新的潜在血管生成抑制剂的盲筛选过程中被选中。在我们的研究中，我们比较了pupupehenone和其他11种相关化合物的潜在抗血管生成活性，这些化合物要么是来自海洋的天然产物，要么是它们的合成衍生物。通过对牛主动脉内皮细胞的生长和分化实验，确定了这些化合物的作用。我们的研究结果表明，这些化合物是细胞生长的弱抑制剂，对内皮细胞没有选择性。然而，与细胞生长相反，当浓度等于或低于3mum时，其中7种化合物完全抑制内皮细胞向管状结构的分化。在CAM实验中，当剂量等于或低于30 nmol/鸡蛋时，其中三种化合物异丙罗、8- epipupehedione和8-epi - 9,11 -二氢pupupehedione完全抑制体内血管生成。进一步的表征表明，这3种萜烯还能抑制内皮细胞的尿激酶生成和侵袭。一种化合物（8- epipupehedione）以剂量依赖性的方式抑制内皮细胞的迁移。所选化合物的抗血管生成特性，其结构的简单性和合成的可行性使其在血管生成相关疾病的治疗中具有进一步评价的吸引力。(C) 2004 Wiley-Liss。公司。
Puupehenone, a sesquiterpene produced by certain sponges, was selected in the course of a blind screening for new potential inhibitors of angiogenesis. In our study, we compare the potential anti-angiogenic activities of puupehenone and another 11 related compounds that were either natural products from marine origin or their synthetic derivatives. The effects of these compounds were determined with cell growth and differentiation assays on bovine aorta endothelial cells. Our results show that these compounds are weak inhibitors to cell growth and are not selective for endothelial cells. However, contrary to cell growth, the differentiation of endothelial cells into tubular structures was completely inhibited by 7 of these compounds at concentrations equal or lower than 3 muM. Three of these compounds, isozonarol, 8-epipuupehedione and 8 epi-9,1 1-dihydropuupehedione, completely inhibited the in vivo angiogenesis in the CAM assay at doses equal or lower than 30 nmol/egg. Further characterisation showed that these 3 terpenes also inhibited endothelial cell production of urokinase and invasion. One compound (8-epipuupehedione) inhibited endothelial cell migration in a dose-dependent manner. The anti-angiogenic properties of the selected compounds, the simplicity of their structures and the feasibility of their synthesis make them attractive drugs for further evaluation in the treatment of angiogenesis-related pathologies. (C) 2004 Wiley-Liss. Inc.