筋骨草甾酮 C | 23044-80-6

• 物质功能分类: 天然产物 - 甾体化合物
• 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
• 中文名称: 筋骨草甾酮 C
• 中文别名: 筋骨草甾酮C
• 英文名称: ajugasterone C
• 英文别名: (2S,3R,5R,9R,10R,11R,13R,14S,17S)-17-[(2R,3R)-2,3-dihydroxy-6-methylheptan-2-yl]-2,3,11,14-tetrahydroxy-10,13-dimethyl-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-6-one
• CAS: 23044-80-6
• 化学式: C₂₇H₄₄O₇
• 分子量: 480.642
• InChiKey: LQGNCUXDDPRDJH-UKTRSHMFSA-N

物化性质

• 沸点：
  677.1±55.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  甲醇（微量）、吡啶（微量）

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  138
• 氢给体数：
  6
• 氢受体数：
  7

制备方法与用途

生物活性

Ajugasterone C 是一种从 Leuzea carthamoides 中分离出来的蜕化类固醇。在100 mg/kg 剂量下，Ajugasterone C 对在Carrageenan-诱导的 Sprague Dawley 大鼠足水肿的发生具有显著的抑制作用。

反应信息

• 作为反应物：
  描述：

  筋骨草甾酮 C 生成 dacryhainansterone
  参考文献：
  名称：

  NIE, RUILIN;QIU, MINHUA, ACTA BOT. YUNNANICA, 9,(1987) N 2, 253-256

  摘要：

  DOI：

文献信息

• Dimeric Ecdysteroid Analogues and Their Interaction with the Drosophila Ecdysteroid Receptor
  作者：Juraj Harmatha、Miloš Buděšínský、Karel Vokáč、Laurence Dinan、René Lafont

  DOI：10.1135/cccc20061229

  日期：——

  Three structurally related specific ecdysteroid derivatives, 7,7'-dimers of 14-deoxy-8(14)-ene transformed 20-hydroxyecdysone, ponasterone A and ajugasterone C, were obtained by photochemical transformation. The structures of the dimeric ecdysteroids were identified mainly by NMR spectroscopy supported by MS and IR spectroscopy. Yields of the dimerisation products were dependent on the reactant concentrations and photoreaction conditions. Inert gas atmosphere supported high yields, whereas oxygen atmosphere fully prevented the dimer formation. All the three dimers retained a rather high agonistic activity at the ecdysteroid receptor in the Drosophila B_II bioassay when compared with the relevant original ecdysteroids.

  三种结构相关的特定类似激素类衍生物，即14-去氧-8(14)-烯类20-羟基脱氧雄甾酮的7,7'-二聚体，通过光化学转化得到，分别为20-羟基脱氧雄甾酮、波纳斯特龙A和阿苏龙C。二聚体激素的结构主要通过核磁共振光谱学鉴定，辅以质谱和红外光谱。二聚体生成产物的产率取决于反应物浓度和光反应条件。惰性气氛支持高产率，而氧气氛完全阻止了二聚体的形成。与相关原始激素相比，在果蝇BII生物检测中，这三种二聚体保留了相当高的激素受体激动活性。
• Squalenoylated Nanoparticle Pro-Drugs of Adjuvant Antitumor 11α-Hydroxyecdysteroid 2,3-Acetonides Act as Cytoprotective Agents Against Doxorubicin and Paclitaxel
  作者：Máté Vágvölgyi、Péter Bélteky、Dóra Bogdán、Márta Nové、Gabriella Spengler、Ahmed D. Latif、István Zupkó、Tamás Gáti、Gábor Tóth、Zoltán Kónya、Attila Hunyadi

  DOI：10.3389/fphar.2020.552088

  日期：——

  In this work, ajugasterone C 2,3;20,22-diacetonide (3) and 11α-hydroxypoststerone 2,3-acetonide (4) were squalenoylated to obtain two new ecdysteroid pro-drugs (6 and 7) and their nano-assemblies (6NP and 7NP). A complete NMR signal assignment of 6 and 7 was achieved. Interaction of compounds 3 and 4 with chemotherapeutics was studied by the Chou-Talalay method. Compound 3 showed strong synergism with

  几种蜕皮类固醇丙酮化物可作为针对各种癌细胞系的辅助化学增敏剂，它们可通过与角鲨烯的可水解缀合配制成自组装的纳米颗粒（NP）前药。在血流中，这种角鲨烯化的纳米颗粒会溶解到低密度脂蛋白（LDL）中，从而可以靶向含有高水平LDL受体的组织。在这项工作中，金刚烷酮C 2,3; 20,22-二烯酮（3）和11α-羟基孕甾酮2,3-丙酮（4）被角鲨烯化，以获得两种新的蜕皮甾类前药（6 和 7）及其纳米组件（6 NP 和 7 NP）。的完整NMR信号分配6 和 7已实现。化合物的相互作用3 和 4通过Chou-Talalay方法研究了化疗药物的使用。复合3在多药耐药性淋巴瘤细胞系中显示出与阿霉素的强协同作用。相反，其纳米组装6 NP明显降低了阿霉素对这些MDR细胞的细胞毒性，强烈表明在前药胞吞后，至少2,3-丙酮化物基团被溶酶体的酸性pH裂解。此外，复合4 与紫杉醇对MCF-7细胞及其纳米物质具有强拮抗作用
• Diversity-Oriented Synthesis Catalyzed by Diethylaminosulfur-Trifluoride—Preparation of New Antitumor Ecdysteroid Derivatives
  作者：Máté Vágvölgyi、Endre Kocsis、Márta Nové、Nikoletta Szemerédi、Gabriella Spengler、Zoltán Kele、Róbert Berkecz、Tamás Gáti、Gábor Tóth、Attila Hunyadi

  DOI：10.3390/ijms23073447

  日期：——

  pharmaceutical chemistry. Diethylaminosulfur-trifluoride (DAST) is a reagent commonly used for replacement of alcoholic hydroxyl groups with fluorine and is also known to catalyze water elimination and cyclic Beckmann-rearrangement type reactions. In this work we aimed to use DAST for diversity-oriented semisynthetic transformation of natural products bearing multiple hydroxyl groups to prepare new bioactive

  氟代表了药物化学中的特殊成分。二乙氨基三氟化硫 (DAST) 是一种常用于用氟取代醇羟基的试剂，也已知可催化水消除和循环贝克曼重排型反应。在这项工作中，我们旨在使用 DAST 对带有多个羟基的天然产物进行面向多样性的半合成转化，以制备新的生物活性化合物。四种蜕皮激素，包括Cyanotis arachnoidea的一种新成分, 被选为 DAST 催化转化的起始材料。新制备的化合物代表了已知 DAST 催化的各种结构变化的组合，以及首次发现的独特的环丙烷闭环。几种化合物在体外表现出抗肿瘤特性。一种新的 17 - N-乙酰蜕皮激素 ( 13 ) 对药物敏感和多药耐药的小鼠 T 细胞淋巴瘤细胞具有有效的抗增殖活性且无细胞毒性。此外，化合物13与阿霉素具有显着的协同作用，而没有可检测到的直接 ABCB1 抑制作用。我们的研究结果表明，DAST 是面向多样性的合成的多功能工具，可将化学空间扩展到新的生物活性化合物。
• Significant Activity of Ecdysteroids on the Resistance to Doxorubicin in Mammalian Cancer Cells Expressing the Human ABCB1 Transporter
  作者：Ana Martins、Noémi Tóth、Attila Ványolós、Zoltán Béni、István Zupkó、József Molnár、Mária Báthori、Attila Hunyadi

  DOI：10.1021/jm300424n

  日期：2012.6.14

  Multidrug resistance (MDR) is a major cause of failure of cancer chemotherapy. Fifty-eight ecdysteroids, herbal analogues of the insect molting hormone and their semisynthetic derivatives, were tested for their activity against L5178 mouse T-cell lymphoma cells (non-MDR) and their subcell line transfected with pHa MDR1/A retrovirus overexpressing the human ABCB1 efflux pump (MDR cell line). The compounds showed very low antiproliferative activities but modulated the efflux of rhodamine 123 mediated by the ABCB1 transporter. Roughly depending on the polarity, mild to strong synergism or antagonism was observed by combining ecdysteroids with doxorubicin, and specific structure-activity relationships were also found. Our results show the effect of ecdysteroids on MDR cancer cells for the first time. Less polar derivatives may serve as valuable leads toward a potent and safe resistance modulator. Biological significance of the resistance-increasing activity of the most abundant phytoecdysteroids including 20-hydroxyecdysone is yet to be clarified.
• Ecdysteroid Derivatives that Reverse P-Glycoprotein-Mediated Drug Resistance
  作者：Roberta Bortolozzi、Andrea Luraghi、Elena Mattiuzzo、Alessandro Sacchetti、Alessandra Silvani、Giampietro Viola

  DOI：10.1021/acs.jnatprod.0c00334

  日期：2020.8.28

  The expression of multidrug resistance P-glycoprotein (P-gp) by cancer cells represents one of the major drawbacks to successful cancer therapy. Accordingly, the development of drugs that inhibit the activity of this transporter remains a major challenge in cancer drug discovery. In this context, several new ecdysteroid derivatives have been synthesized and evaluated as P-gp inhibitors. Two of them (compounds 9 and 14) were able to resensitize CEMVbl100 and LoVo(Doxo) resistant cell lines to vinblastine and doxorubicin, respectively. Indeed, both compounds 9 and 14 increased the cellular accumulation of rhodamine 123 in cells expressing P-gp and stimulated basal P-glycoprotein-ATPase activity at a 1 mu M concentration, demonstrating their interference with the transport of other substrates in a competitive mode. Moreover, in a medulloblastoma cell line (DAOY), compounds 9 and 14 reduced the side population representing cancer stem cells, which are characterized by a high expression of ABC drug transporters. Further, in DAOY cells, the same two compounds synergized with cisplatin and vincristine, two drugs used commonly in the therapy of medulloblastoma. Molecular docking studies on the homology-modeled structure of the human P-glycoprotein provided a rationale for the biological results, validating the binding mode within the receptor site, in accordance with lipophilicity data and observed structure-activity relationship information. Altogether, the present results endorse these derivatives as promising P-gp inhibitors, and they may serve as candidates to reverse drug resistance in cancer cells.