二氢乌本箭毒苷 | 1183-35-3

• 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: 二氢乌本箭毒苷
• 中文别名: 二氢乌本(箭毒)苷
• 英文名称: dihydroouabain
• 英文别名: 4-[(1R,3S,5S,8R,9S,10R,11R,13R,14S,17R)-1,5,11,14-tetrahydroxy-10-(hydroxymethyl)-13-methyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]oxolan-2-one
• CAS: 1183-35-3
• 化学式: C₂₉H₄₆O₁₂
• 分子量: 586.677
• InChiKey: ZTFGOPUOTATSAL-CFVDWFIMSA-N

物化性质

• 熔点：
  168-170 °C
• 沸点：
  827.7±65.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  41
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  207
• 氢给体数：
  8
• 氢受体数：
  12

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  T
• 危险类别码：
  R23/24/25
• 危险品运输编号：
  UN 1544
• WGK Germany：
  3
• RTECS号：
  FH4551000
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 安全说明：
  S36/37/39,S45
• 危险标志：
  GHS06
• 危险性描述：
  H301 + H331
• 危险性防范说明：
  P261,P304 + P340 + P312,P403 + P233

反应信息

• 作为产物：
  描述：

  G毒毛旋花苷 在 水 、 钯 作用下， 生成 二氢乌本箭毒苷
  参考文献：
  名称：

  Jacobs; Hoffmann, Journal of Biological Chemistry, 1927, vol. 74, p. 787,792

  摘要：

  DOI：

文献信息

• Discovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins
  作者：Nitzan Koppel、Jordan E Bisanz、Maria-Eirini Pandelia、Peter J Turnbaugh、Emily P Balskus

  DOI：10.7554/elife.33953

  日期：——

  Although the human gut microbiome plays a prominent role in xenobiotic transformation, most of the genes and enzymes responsible for this metabolism are unknown. Recently, we linked the two-gene ‘cardiac glycoside reductase’ (cgr) operon encoded by the gut Actinobacterium Eggerthella lenta to inactivation of the cardiac medication and plant natural product digoxin. Here, we compared the genomes of 25 E. lenta strains and close relatives, revealing an expanded 8-gene cgr-associated gene cluster present in all digoxin metabolizers and absent in non-metabolizers. Using heterologous expression and in vitro biochemical characterization, we discovered that a single flavin- and [4Fe-4S] cluster-dependent reductase, Cgr2, is sufficient for digoxin inactivation. Unexpectedly, Cgr2 displayed strict specificity for digoxin and other cardenolides. Quantification of cgr2 in gut microbiomes revealed that this gene is widespread and conserved in the human population. Together, these results demonstrate that human-associated gut bacteria maintain specialized enzymes that protect against ingested plant toxins.

  尽管人类肠道微生物组在异生物转化中发挥着重要作用，但负责这种代谢的大多数基因和酶却不为人知。最近，我们将肠道放线菌（Eggerthella lenta）编码的双基因 "强心苷还原酶"（gr）操作子与强心药物和植物天然产物地高辛的灭活联系起来。在这里，我们比较了 25 个伦塔放线杆菌菌株和近亲的基因组，发现所有地高辛代谢菌中都存在一个扩展的 8 基因 cgr 相关基因簇，而非代谢菌中则不存在。通过异源表达和体外生化鉴定，我们发现一个依赖于黄素和[4Fe-4S]簇的还原酶Cgr2足以使地高辛失活。意想不到的是，Cgr2 对地高辛和其他贲门醇类化合物具有严格的特异性。对肠道微生物组中的 Cgr2 进行定量分析后发现，该基因在人类中广泛存在且具有保守性。这些结果共同证明，与人类相关的肠道细菌保持着专门的酶，可防止摄入植物毒素。
• Cardiac Glycoside Activities Link Na⁺/K⁺ ATPase Ion-Transport to Breast Cancer Cell Migration via Correlative SAR
  作者：Anniefer N. Magpusao、George Omolloh、Joshua Johnson、José Gascón、Mark W. Peczuh、Gabriel Fenteany

  DOI：10.1021/cb500665r

  日期：2015.2.20

  The cardiac glycosides ouabain and digitoxin, established Na(+)/K(+) ATPase inhibitors, were found to inhibit MDA-MB-231 breast cancer cell migration through an unbiased chemical genetics screen for cell motility. The Na(+)/K(+) ATPase acts both as an ion-transporter and as a receptor for cardiac glycosides. To delineate which function is related to breast cancer cell migration, structure-activity relationship (SAR) profiles of cardiac glycosides were established at the cellular (cell migration inhibition), molecular (Na(+)/K(+) ATPase inhibition), and atomic (computational docking) levels. The SAR of cardiac glycosides and their analogs revealed a similar profile, a decrease in potency when the parent cardiac glycoside structure was modified, for each activity investigated. Since assays were done at the cellular, molecular, and atomic levels, correlation of SAR profiles across these multiple assays established links between cellular activity and specific protein-small molecule interactions. The observed antimigratory effects in breast cancer cells are directly related to the inhibition of Na(+)/K(+) transport. Specifically, the orientation of cardiac glycosides at the putative cation permeation path formed by transmembrane helices αM1-M6 correlates with the Na(+) pump activity and cell migration. Other Na(+)/K(+) ATPase inhibitors that are structurally distinct from cardiac glycosides also exhibit antimigratory activity, corroborating the conclusion that the antiport function of Na(+)/K(+) ATPase and not the receptor function is important for supporting the motility of MDA-MB-231 breast cancer cells. Correlative SAR can establish new relationships between specific biochemical functions and higher-level cellular processes, particularly for proteins with multiple functions and small molecules with unknown or various modes of action.
• DE1147222
  申请人：——

  公开号：——

  公开（公告）日：——
• Jacobs; Hoffmann, Journal of Biological Chemistry, 1927, vol. 74, p. 787,792
  作者：Jacobs、Hoffmann

  DOI：——

  日期：——