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Microwave-assisted green synthesis of bile acid derivatives and evaluation of glucocorticoid receptor binding
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2020-11-19 , DOI: 10.1039/d0md00311e
Bojana R Vasiljević 1 , Edward T Petri 2 , Sofija S Bekić 1 , Andjelka S Ćelić 2 , Ljubica M Grbović 1 , Ksenija J Pavlović 1
Affiliation  

Herein, we present microwave-assisted AlCl3 catalyzed oxidation of bile acid hydroxyl groups in the presence of Oxone® in water media. Significant rate enhancements were observed for Wolff–Kishner reduction of synthesized bile acids oxo derivatives to the 5β-cholanic acid. Reaction of amidation of the simplest bile acid and aminolysis of the deoxycholic acid was accomplished in the absence of solvent and catalysts under sealed vessel microwave conditions. Because 5β-cholanic acid reportedly modulates glucocorticoid receptor signaling in cell models of Parkinson's disease, we tested the affinity of 5β-cholanic acid and deoxycholic acid derivatives for the glucocorticoid receptor in vitro using a yeast-based fluorescent screen. Treatment of GR-expressing yeast with prednisolone resulted in a dose-dependent increase in fluorescence; whereas 5β-cholanic acid binds to the glucocorticoid receptor with more moderate affinity. Similarly, molecular docking also suggests that 5β-cholanic acid can bind to the glucocorticoid receptor, with similar geometry to known GR ligands.

中文翻译:

胆汁酸衍生物的微波辅助绿色合成及糖皮质激素受体结合评价

在此,我们展示了在水介质中存在 Oxone® 的情况下,微波辅助 AlCl 3催化的胆汁酸羟基氧化。观察到 Wolff-Kishner 将合成的胆汁酸氧代衍生物还原为 5β-胆酸的速率显着提高。最简单的胆汁酸的酰胺化反应和脱氧胆酸的氨解反应是在没有溶剂和催化剂的情况下在密封容器微波条件下完成的。因为据报道 5β-胆酸在帕金森病细胞模型中调节糖皮质激素受体信号传导,我们在体外测试了 5β-胆酸和脱氧胆酸衍生物对糖皮质激素受体的亲和力使用基于酵母的荧光屏幕。用泼尼松龙处理表达 GR 的酵母导致荧光的剂量依赖性增加;而 5β-胆酸以更温和的亲和力与糖皮质激素受体结合。同样,分子对接也表明 5β-胆酸可以与糖皮质激素受体结合,与已知的 GR 配体具有相似的几何形状。
更新日期:2021-01-12
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