The solution behavior of auranofin, Et₃PAuCl and Et₃PAuI, as well as their interactions with hen egg white lysozyme, single strand oligonucleotide, and ds-DNA were comparatively analyzed through NMR spectroscopy, ESI-MS, ethidium bromide displacement, DNA melting and viscometric tests. The cytotoxic effects toward representative colorectal cancer cell lines were found to be strong and similar in the three cases and a good correlation could be established between the cytotoxicity and the ability to inhibit thioredoxin reductase; remarkably, in vivo acute toxicity experiments for Et₃PAuI confirmed that, similarly to auranofin, this drug is well tolerated in a murine model. Overall, a very similar profile emerges for Et₃PAuI and Et₃PAuCl, which retain the potent cytotoxic effects of auranofin while showing some peculiar features. These results demonstrate that the presence of the thiosugar moiety is not mandatory for the pharmacological action, suggesting that the tuning of some relevant chemical properties such as lipophilicity could be exploited to improve bioavailability, with no loss of the pharmacological effects.

中文翻译：

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Auranofin ，Et ₃ PAuCl和Et ₃ PAuI对结直肠癌细胞具有高度细胞毒性：化学和生物学研究

通过NMR光谱，ESI-MS，溴化乙锭置换，DNA熔解比较分析了金诺芬，Et ₃ PAuCl和Et ₃ PAuI的溶液行为，以及它们与鸡蛋清溶菌酶，单链寡核苷酸和ds-DNA的相互作用。和粘度测试。在这三种情况下，发现对代表性的结直肠癌细胞系的细胞毒性作用强且相似，并且可以在细胞毒性与抑制硫氧还蛋白还原酶的能力之间建立良好的相关性。值得注意的是，针对Et ₃ PAuI的体内急性毒性实验证实，与金诺芬类似，该药物在鼠模型中具有良好的耐受性。总体而言，Et ₃出现了非常相似的配置文件PAuI和Et ₃ PAuCl保留了金诺芬的强力细胞毒性作用，同时表现出一些独特的功能。这些结果表明，硫糖基部分的存在对于药理作用不是强制性的，表明可以利用某些相关化学性质如亲脂性的调节来改善生物利用度，而不会损失药理作用。