20-hydroxyecdysone 2,3,22,25-tetraacetate

• 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: 20-hydroxyecdysone 2,3,22,25-tetraacetate
• 英文别名: ecdysterone 2,3,22,25-tetraacetate；Crustecdyson-2,3,22,25-tetraacetat (Viticosteron E-2,3,22-triacetat)；[(2S,3R,5R,9R,10R,13R,14S,17S)-2-acetyloxy-17-[(2R,3R)-3,6-diacetyloxy-2-hydroxy-6-methylheptan-2-yl]-14-hydroxy-10,13-dimethyl-6-oxo-2,3,4,5,9,11,12,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-3-yl] acetate
• 化学式: C₃₅H₅₂O₁₁
• 分子量: 648.791
• InChiKey: XFZQCCONUDJVNN-RGTQMJDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  蜕皮激素 、 乙酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以67%的产率得到20-hydroxyecdysone 2,3,22,25-tetraacetate
  参考文献：
  名称：

  Ecdysteroid Derivatives that Reverse P-Glycoprotein-Mediated Drug Resistance

  摘要：

  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.

  DOI：

  10.1021/acs.jnatprod.0c00334

文献信息

• Selective acetylation of 20-hydroxyecdysone partial synthesis of some minor ecdysteroids and analogues
  作者：Apichart Suksamrarn、Prasert Pattanaprateep

  DOI：10.1016/0040-4020(95)00635-l

  日期：1995.9

  Selective acetylation of the 2:3- and 20:22-acetonide and 2:3:20,22-diacetonide derivatives of 20-hydroxyecdysone and subsequent removal of the protecting groups led to partial synthesis of a number of mono-, di- and triacetate derivatives of 20-hydroxyecdysone. Some of these acetate derivatives are minor, naturally occurring ecdysteroids.

  20-羟基蜕皮酮的2：3-和20：22-丙酮和2：3：20,22-二烯酮衍生物的选择性乙酰化和随后的保护基的去除导致部分单，双和三价合成20-羟基蜕皮酮的三乙酸酯衍生物。这些乙酸酯衍生物中的一些是次要的天然蜕皮类固醇。
• ——
  作者：V. N. Syrov、Z. Saatov、Sh. Sh. Sagdullaev、A. U. Mamatkhanov

  DOI：10.1023/a:1015344614064

  日期：——
• Regioselective synthesis of 20-hydroxyecdysone glycosides
  作者：Jaroslav Píš、Jiří Hykl、Miloš Buděšinský、Juraj Harmatha

  DOI：10.1016/s0040-4020(01)85536-8

  日期：1994.1

  Four beta-D-glucopyranosides of 20-hydroxyecdysone (1) were prepared. The regioselective course of glycosylation was achieved by the combination of hydroxyl and 1,2-diol protective groups, i.e. acetates and phenyl boronates, in the aglycone moiety.
• 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.