The combretastatins have attracted significant interest as small‐molecule therapies for cancer due to their ability to function as vascular disrupting agents. We have successfully prepared a range of combretastatin analogues that are based on a novel sydnone heterocycle core, and their potential as tubulin binders has been assessed in vitro and in vivo. The most potent candidate was found to disrupt microtubules and affect cellular morphology at sub‐micromolar levels. Moreover, it was found to bind reversibly to tubulin and significantly increase endothelial cell monolayer permeability, in a similar manner to combretastatin A4. Surprisingly, the compound did not exhibit efficacy in vivo, possibly due to rapid metabolism.

中文翻译：

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评估基于司乃酮的Combretastatin A-4磷酸酯类似物（CA4P）作为血管分裂剂用于癌症治疗

康普他汀作为癌症的小分子疗法已引起人们极大的兴趣，这是因为它们具有血管破裂剂的功能。我们已经成功地制备了一系列基于新型sydnone杂环核心的康布雷他汀类似物，并且已经在体外和体内评估了它们作为微管蛋白结合剂的潜力。发现最有效的候选物可在亚微摩尔水平破坏微管并影响细胞形态。此外，发现以与康维他汀A4相似的方式可逆地结合微管蛋白并显着增加内皮细胞单层通透性。出人意料的是，该化合物在体内没有表现出功效，这可能是由于快速代谢所致。