Bonezzi Katiuscia, Taraboletti Giulia, Borsotti Patrizia, Bellina Fabio, Rossi Renzo, Giavazzi Raffaella
Department of Oncology, Mario Negri Institute for Pharmacological Research, via Gavazzeni 11, 24125 Bergamo, Italy.
J Med Chem. 2009 Dec 10;52(23):7906-10. doi: 10.1021/jm900968s.
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 on the imidazole ring, responsible for greater interaction energy with tubulin and higher cytotoxicity, were not associated to greater vascular disrupting activity.
对具有高细胞毒性的1,5-二芳基-1H-咪唑进行了研究，以阐明细胞毒性与作为血管破坏剂（VDA）的活性之间的关系。所有化合物均破坏了微管蛋白细胞骨架，影响了体外内皮细胞形态和毛细血管形成，并在体内导致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，咪唑环上负责与微管蛋白产生更大相互作用能和更高细胞毒性的取代模式，与更强的血管破坏活性并无关联。
