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Identification of nitric oxide-releasing derivatives of oleanolic acid as potential anti-colon cancer agents

机译：确定齐墩果酸的释放一氧化氮的衍生物作为潜在的抗结肠癌药物

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摘要

A group of nitric oxide (NO)-releasing derivatives of oleanolic acid (OA) (5-13) were designed, synthesized and biologically evaluated for their anti-colon cancer activity. It was found that the most potent compound 6 preferably released high levels of NO in colon cancer cells but not in normal cells, leading to potent cytotoxicity against colon cancer cells. In addition, 6 was more prone to produce NO catalyzed by GSTp relative to GSTa. Furthermore, 6 significantly inhibited the tumor growth in a mouse xenograft model. Finally, 6 induced nitration of tyrosine residues in mitochondrial protein, down-regulated Wnt/b-catenin pathway, and inhibited COX-2 centered signaling loop in colon cancer cells. Collectively, our findings suggested that 6 could be a promising candidate for the intervention of colon cancer.
机译：设计，合成和生物学评估了一组齐墩果酸（OA）的释放一氧化氮（NO）的衍生物的抗结肠癌活性。已经发现，最有效的化合物6优选在结肠癌细胞中而不在正常细胞中释放高水平的NO，从而导致针对结肠癌细胞的有效细胞毒性。此外，相对于GSTa，GSTp催化6生成NO的可能性更高。此外，6在小鼠异种移植模型中显着抑制了肿瘤的生长。最后，6诱导线粒体蛋白中酪氨酸残基的硝化，下调Wnt / b-catenin途径，并抑制结肠癌细胞中以COX-2为中心的信号转导。总的来说，我们的发现表明6可能是结肠癌干预的有希望的候选者。

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