Vascular Disrupting Activity of Tubulin-Binding 1,5-Diaryl-1H-imidazoles
Vascular Disrupting Activity of Tubulin-Binding 1,5-Diaryl-1H-imidazoles
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DOI：
10.1021/jm900968s
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发表时间：
2009-12-10
影响因子：
7.3
通讯作者：
Giavazzi, Raffaella
中科院分区：
文献类型：
--
作者：
Bonezzi, Katiuscia;Taraboletti, Giulia;Giavazzi, Raffaella
研究了高细胞毒性1,5-二芳基- 1h -咪唑，以阐明细胞毒性与血管破坏剂（VDA）活性之间的关系。所有化合物在体外破坏微管蛋白细胞骨架，影响内皮细胞形态和毛细血管形成，在体内引起血管关闭和肿瘤坏死，从而证实了它们的血管破坏特性。尽管如此，咪唑环上的取代模式与微管蛋白具有更大的相互作用能量和更高的细胞毒性，但与更大的血管破坏活性无关。
Highly cytotoxic 1,5-diaryl-1H-imidazoles were studied to clarify the relationship between cytotoxicity and activity as vascular disrupting agents (VDA). All the compounds disorganized the tubulin cytoskeleton, affected endothelial cell morphology and capillary formation in vitro, and caused vessel shutdown and tumor necrosis in vivo, thus confirming their vascular disrupting properties. Nonetheless, the substitution patterns oil the imidazole ring, responsible for greater interaction energy with tubulin and higher cytotoxicity, were not associated to greater vascular disrupting activity.