N(1a),N'(1a)-(1,4-butanedionyl)dimitomycin C

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N(1a),N'(1a)-(1,4-butanedionyl)dimitomycin C
• 英文别名: [(4S,6S,7R,8S)-11-amino-5-[4-[(4S,6S,7R,8S)-11-amino-8-(carbamoyloxymethyl)-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-5-yl]-4-oxobutanoyl]-7-methoxy-12-methyl-10,13-dioxo-2,5-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),11-dien-8-yl]methyl carbamate
• 化学式: C₃₄H₃₈N₈O₁₂
• 分子量: 750.722
• InChiKey: AVRDKFWXHPHEFM-VSSZRIIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  54
• 可旋转键数：
  11
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  290
• 氢给体数：
  4
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  丁二酰氯 、 mitomycin C 在 TEA 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以35%的产率得到N(1a),N'(1a)-(1,4-butanedionyl)dimitomycin C
  参考文献：
  名称：

  Synthesis, DNA Cross-Linking Activity, and Cytotoxicity of Dimeric Mitomycins

  摘要：

  Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C(1) itself is the prototypical bioreductive DNA cross-linking agent. DNA cross-linking experiments using a denaturing-gel-electrophoresis-based assay showed that the extent of DNA cross-linking for select dimeric mitomycins can exceed that of the parent compound, mitomycin C, and that the reaction proceeds, in part, at the two distal C(l) sites in the mitomycins. The efficiency of DNA cross-linking depended on the nature of the linker and the position of linker unit's attachment. When we compared the efficiency of DNA cross-linking for the dimeric mitomycins with their in vitro cytotoxicities in cultured human tumor cells, we observed a poor correlation. The mitomycins that gave the highest levels of DNA cross-linked adducts displayed the weakest cytotoxicities. These findings determined that the denaturing-gel-electrophoresis-based assay was a poor predictor of cytotoxic activity.

  DOI：

  10.1021/jm010090y

文献信息

• Synthesis, DNA Cross-Linking Activity, and Cytotoxicity of Dimeric Mitomycins
  作者：Younghwa Na、Ven-Shun Li、Yuka Nakanishi、Kenneth F. Bastow、Harold Kohn

  DOI：10.1021/jm010090y

  日期：2001.10.1

  Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C(1) itself is the prototypical bioreductive DNA cross-linking agent. DNA cross-linking experiments using a denaturing-gel-electrophoresis-based assay showed that the extent of DNA cross-linking for select dimeric mitomycins can exceed that of the parent compound, mitomycin C, and that the reaction proceeds, in part, at the two distal C(l) sites in the mitomycins. The efficiency of DNA cross-linking depended on the nature of the linker and the position of linker unit's attachment. When we compared the efficiency of DNA cross-linking for the dimeric mitomycins with their in vitro cytotoxicities in cultured human tumor cells, we observed a poor correlation. The mitomycins that gave the highest levels of DNA cross-linked adducts displayed the weakest cytotoxicities. These findings determined that the denaturing-gel-electrophoresis-based assay was a poor predictor of cytotoxic activity.