N-(N-retinoyl)-L-leucyldoxorubicin 14-linoleate | 94731-66-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-(N-retinoyl)-L-leucyldoxorubicin 14-linoleate
• CAS: 94731-66-5
• 化学式: C₇₁H₉₈N₂O₁₃
• 分子量: 1187.56
• InChiKey: APIQABWLMGIABO-CEUVVVEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.41
• 重原子数：
  86.0
• 可旋转键数：
  30.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  227.25
• 氢给体数：
  6.0
• 氢受体数：
  13.0

反应信息

• 作为产物：
  描述：

  维A酸 在 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 64.0h， 生成 N-(N-retinoyl)-L-leucyldoxorubicin 14-linoleate
  参考文献：
  名称：

  Selective uptake of a toxic lipophilic anthracycline derivative by the low density lipoprotein receptor pathway in cultured fibroblasts

  摘要：

  N-(N-Retinoyl)-L-leucyldoxorubicin 14-linoleate (r11-DOX), a new lipophilic derivative of doxorubicin, was synthesized and incorporated into low-density lipoprotein (LDL). The drug-LDL complex contained 100-200 drug molecules/LDL particle. When cultured normal human fibroblasts were incubated with 125I-LDL-incorporated drug, there was a perfect correlation between the cellular uptake plus degradation of 125I-LDL and the cellular drug accumulation. The presence of excess native LDL inhibited the cellular uptake and degradation of 125I-LDL and the drug accumulation to the same extent. In contrast, methylated LDL, which does not bind to the LDL receptor, did not alter the cellular uptake and degradation of 125I-LDL nor did it alter the drug accumulation. When LDL receptor negative fibroblasts from a patient with the homozygous form of familial hypercholesterolemia were incubated with the drug-125I-LDL complex, cellular drug accumulation was very low. The drug-LDL complex inhibited the growth of cultured normal human fibroblasts. The drug incorporated into methylated LDL was much less toxic. These findings suggest that r11-DOX incorporated into LDL is delivered to cells selectively by the LDL receptor pathway. This might be of value in the treatment of leukemia, since we have previously found that leukemic cells exhibit higher LDL receptor activity than white blood cells and bone marrow cells from healthy subjects.

  DOI：

  10.1021/jm00382a011