18-β-Glycyrrhetinic acid (GA; 1) and many of its derivatives are cytotoxic in cancer cells. The current study aims to characterize the anticancer effects of 17 novel 1 derivatives. On the basis of these studies, N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b) appeared to be the most potent compound, with IC₅₀in vitro growth inhibitory concentrations in single-digit micromolarity in a panel of 8 cancer cell lines. Compound 6b is cytostatic and displays similar efficiency in apoptosis-sensitive versus apoptosis-resistant cancer cell lines through, at least partly, the inhibition of the activity of a cluster of a dozen kinases that are implicated in cancer cell proliferation and in the control of the actin cytoskeleton organization. Compound 6b also inhibits the activity of the 3 proteolytic units of the proteasome. Compound 6b thus represents an interesting hit from which future compounds could be derived to improve chemotherapeutic regimens that aim to combat cancers associated with poor prognoses.

中文翻译：

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N-（2- {3- [3,5-双（三氟甲基）苯基]脲基}乙基）-甘草次酸酰胺（6b）：靶向蛋白酶体并显示抗激酶活性的新型抗癌甘草次酸衍生物

18-β-甘草次酸（GA; 1）及其许多衍生物在癌细胞中具有细胞毒性。当前的研究旨在表征17种新型1衍生物的抗癌作用。在这些研究的基础上，N-（2- {3- [3,5-双（三氟甲基）苯基]脲基}乙基）-甘草次氨酰胺（6b）似乎是最有效的化合物，对IC ₅₀的体外生长抑制作用一组8个癌细胞系中的单位浓度微摩尔浓度。化合物6b具有抑制癌细胞生长的作用，并且至少部分地通过抑制与癌细胞增殖和肌动蛋白细胞骨架有关的十几种激酶簇的活性，在凋亡敏感性和凋亡抵抗性癌细胞系中显示出相似的效率。组织。化合物6b还抑制蛋白酶体的3个蛋白水解单元的活性。因此，化合物6b代表了一个有趣的命题，从中可以衍生出未来的化合物以改善旨在对抗与不良预后相关的癌症的化疗方案。