(2S,3R)-3-[[(2S)-2-[[(4S)-4-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[2-[[(2S,3S)-2-hydroxy-3-methylpentanoyl]amino]acetyl]-methylamino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-methylbutanoyl]-methylamino]-3-phenylpropanoyl]amino]-2,2-dimethyl-3-oxopentanoyl]amino]propanoyl]amino]-2-methylpentanoic acid | 1163684-87-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2S,3R)-3-[[(2S)-2-[[(4S)-4-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[2-[[(2S,3S)-2-hydroxy-3-methylpentanoyl]amino]acetyl]-methylamino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-methylbutanoyl]-methylamino]-3-phenylpropanoyl]amino]-2,2-dimethyl-3-oxopentanoyl]amino]propanoyl]amino]-2-methylpentanoic acid
• CAS: 1163684-87-4
• 化学式: C₄₉H₈₀N₈O₁₂
• 分子量: 973.221
• InChiKey: RHNKFTFBLMRTMD-XPQZGKFDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  69
• 可旋转键数：
  28
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  281
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  desmethoxymajusculamide C 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以98%的产率得到(2S,3R)-3-[[(2S)-2-[[(4S)-4-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[2-[[(2S,3S)-2-hydroxy-3-methylpentanoyl]amino]acetyl]-methylamino]-3-methylpentanoyl]amino]acetyl]-methylamino]-3-methylbutanoyl]-methylamino]-3-phenylpropanoyl]amino]-2,2-dimethyl-3-oxopentanoyl]amino]propanoyl]amino]-2-methylpentanoic acid
  参考文献：
  名称：

  Desmethoxymajusculamide C, a Cyanobacterial Depsipeptide with Potent Cytotoxicity in Both Cyclic and Ring-Opened Forms

  摘要：

  Cytotoxicity-guided fractionation of the organic extract from a Fijian Lyngbya majuscula led to the discovery of desmethoxymajusculamide C (DMMC) as the active metabolite. Spectroscopic analysis including 1D and 2D NMR, MS/MS, and chemical degradation and derivatization protocols were used to assign the planar structure and stereoconfiguration of this new cyclic depsipeptide. DMMC demonstrated potent and selective anti-solid tumor activity with an IC50 = 20 nM against the HCT-116 human colon carcinoma cell line via disruption of cellular microfilament networks. A linear form of DMMC was generated by base hydrolysis, and the amino acid sequence was confirmed by mass spectrometry. Linearized DMMC was also evaluated in the biological assays and found to maintain potent actin depolymerization characteristics while displaying solid tumor selectivity equivalent to DMMC in the disk diffusion assay. A clonogenic assay assessing cytotoxicity to HCT-116 cells as a function of exposure duration showed that greater than 24 h of constant drug treatment was required to yield significant cell killing. Therapeutic studies with HCT-116 bearing SCID mice demonstrated efficacy at the highest dose used (%T/C = 60% at 0.62 mg/kg daily for 5 days).

  DOI：

  10.1021/np9001674