9(11),(5β)-cholenic acid-3α-ol-12-one | 6874-18-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 9(11),(5β)-cholenic acid-3α-ol-12-one
• 英文别名: 9(11), 5β cholenic acid 3α ol 12 one；3α-hydroxy-12-oxo-5β-chol-9(11)-en-24-oic acid；3α-Hydroxy-12-oxo-5β-chol-9(11)-en-24-saeure；3α-Hydroxy-12-oxo-5β-cholen-(9(11))-saeure-(24)；3α-Hydroxy-Δ⁹⁽¹¹⁾-12-oxo-cholensaeure；3-Hydroxy-12-oxo-Δ⁹-cholensaeure；3alpha-Hydroxy-12-oxo-5beta-chol-9(11)-en-24-oic Acid；(4R)-4-[(3R,5R,8S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-12-oxo-1,2,3,4,5,6,7,8,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 6874-18-6
• 化学式: C₂₄H₃₆O₄
• 分子量: 388.547
• InChiKey: RMEZJKHOZLUOHB-OZEXFWQTSA-N

物化性质

• 沸点：
  564.3±50.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9(11),(5β)-cholenic acid-3α-ol-12-one 在 重氮甲烷 、 吡啶 、 乙醚 作用下， 生成 3a-乙酰氧基-12-氧代-5b-胆-9(11)-烯-24-酸甲酯
  参考文献：
  名称：

  Effects of Bcl-2 modulation with G3139 antisense oligonucleotide on human breast cancer cells are independent of inherent Bcl-2 protein expression

  摘要：

  We have investigated the effects of transient Bcl-2 down-regulation induced by the Bcl-2 antisense oligodeoxynucleotide (ODN) G3139 (Genta Incorporated) in high Bcl-2 protein expressing, estrogen receptor (ER) positive MCF-7 and low Bcl-2 expressing, ER negative MDA435/LCC6 human breast cancer cells. Treatment with Bcl-2 antisense ODN in vitro caused > 80% reduction of Bcl-2 protein levels in a sequence specific manner for both cell lines. Maximum mRNA reduction was achieved within 24 h of the first antisense ODN exposure whereas full protein down-regulation required antisense exposure over 48 h. This Bcl-2 reduction was associated with 80-95% loss of viable cells compared to untreated cells. Similar cytotoxic effects were observed in both cell lines despite a nine-fold intrinsic difference in Bcl-2 protein expression suggesting that the relative degree of down-regulation of Bcl-2 is more important than the absolute reduction. Cell death associated with G3139 exposure exhibited properties indicative of apoptosis such as mitochondrial membrane depolarization and caspase activation. Combined treatment with G3139 and cytotoxic agents resulted in additive cytotoxicity in both cell lines. However, under most conditions studied, the direct cytotoxic activity of G3139 antisense was not synergistic with the cytotoxic agents. These results suggest that while Bcl-2 clearly constitutes an attractive therapeutic target due to its role in regulating apoptosis in breast cancer cells, additional mechanisms are important in the control of apoptosis arising from exposure to anticancer agents in vitro.

  DOI：

  10.1023/a:1017371013487
• 作为产物：
  描述：

  3α-acetoxy-12-oxo-5β-cholanoic acid-(24) 在 重氮甲烷 、 吡啶 、 氢氧化钾 、 乙醚 、 氢溴酸 、 溴 、 溶剂黄146 作用下， 生成 9(11),(5β)-cholenic acid-3α-ol-12-one
  参考文献：
  名称：

  ÜberGallensäuren和veroffdte Stoffe。21.米特隆。3α-乙酰氧基-12-酮-胆碱-（9）-säure和3α-乙氧基-胆粉-（9）-säure

  摘要：

  DOI：

  10.1002/hlca.19430260218

文献信息

• Screening the binding affinity of bile acid derivatives for the glucocorticoid receptor ligand-binding domain
  作者：Srdjan Bjedov、Sofija Bekic、Maja Marinovic、Dusan Skoric、Ksenija Pavlovic、Andjelka Celic、Edward Petri、Marija Sakac

  DOI：10.2298/jsc220912078b

  日期：——

  The necessity of anti-inflammatory drugs such as glucocorticoids has been evident during the COVID-19 pandemic. Glucocorticoids, are the standard therapy for the treatment of moderate and severe COVID-19 patients. However, serious side effects limit the use of these drugs, and anti-inflammatory drugs with better pharmacological properties are urgently required. Bile acids are of interest, because of their anti-inflammatory and immunomodulatory properties, facilitated through an unclear mechanism involving transmembrane and nuclear receptors. In this work, we screened the binding activity of a number of bile acid derivatives, for the ligand-binding domain of glucocorticoid receptor (GR-LBD), the most important receptor for anti-inflammatory processes. Tested compounds include oximes, lactones, lactams, tetrazoles, dienones, C-24 alcohols and cholic acid amides. Cholic acid oxime, deoxycholic acid dienone, 3-keto-24-cholic alcohol and cholic acid amide showed best binding affinities for GR-LBD among tested compounds. The in silico molecular docking explanation is provided. SAR analysis showed that expansion of B and C steroid rings or attachment of heterocycle to C ring is not beneficial for binding; side chain should contain hydrogen donor group; the GR-LBD tolerate well different functionalities on C-3 position. These results provide valuable information toward synthesis of the new glucocorticoids based on bile acids.

  在 COVID-19 大流行期间，糖皮质激素等抗炎药物的必要性显而易见。糖皮质激素是治疗中度和重度 COVID-19 患者的标准疗法。然而，严重的副作用限制了这些药物的使用，因此迫切需要药理特性更好的抗炎药物。胆汁酸具有抗炎和免疫调节特性，其机制尚不明确，涉及跨膜受体和核受体，因此备受关注。在这项工作中，我们筛选了一些胆汁酸衍生物与糖皮质激素受体（GR-LBD）配体结合域的结合活性，糖皮质激素受体是抗炎过程中最重要的受体。受测化合物包括肟类、内酯类、内酰胺类、四唑类、二烯酮类、C-24 醇类和胆酸酰胺类。在测试的化合物中，胆酸肟、脱氧胆酸二烯酮、3-酮基-24-胆酸醇和胆酸酰胺与 GR-LBD 的结合亲和力最佳。本研究提供了硅学分子对接解释。SAR 分析表明，类固醇 B 环和 C 环的扩展或杂环与 C 环的连接不利于结合；侧链应包含氢供体基团；GR-LBD 能很好地耐受 C-3 位置上的不同官能团。这些结果为基于胆汁酸合成新的糖皮质激素提供了有价值的信息。
• Ruff et al., Journal of the Chemical Society, 1953, p. 3683,3687
  作者：Ruff et al.

  DOI：——

  日期：——
• Turner et al., Journal of Biological Chemistry, 1946, vol. 162, p. 571,573
  作者：Turner et al.

  DOI：——

  日期：——
• Sarett, Journal of Biological Chemistry, 1946, vol. 162, p. 601,6307
  作者：Sarett

  DOI：——

  日期：——
• �ber Gallens�uren und verwandte Stoffe. 21. Mitteilung. 3?-Acetoxy-12-keto-cholen-(9)-s�ure und 3?-Oxy-cholen-(9)-s�ure
  作者：E. Seebeck、T. Reichstein

  DOI：10.1002/hlca.19430260218

  日期：1943.3.15