Proline-Methotrexate | 154508-79-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Proline-Methotrexate
• 英文别名: Pro-MTX
• CAS: 154508-79-9
• 化学式: C₂₅H₂₉N₉O₆
• 分子量: 551.562
• InChiKey: KRUBMRPVVPVHKH-IRXDYDNUSA-N

物化性质

• 密度：
  1.520±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.26
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  230.85
• 氢给体数：
  5.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  Fmoc-Pro-NovaSyn TGT resin 、 2,4-diaminopteroic acid hemihydrochloride 、 Fmoc-O-叔丁基-L-谷氨酸 在 哌啶 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 以45%的产率得到Proline-Methotrexate
  参考文献：
  名称：

  Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231 cells

  摘要：

  The resistance to methotrexate by a number of cancer cells such as breast cancer cell-line MDA-MB-231 due to poor permeability renders it less effective as an anticancer agent for these cells. Proline prodrug of methotrexate (Pro-MTX) was designed as a substrate of prolidase which is specific for imido bond of dipeptide containing proline and expected to penetrate MDA-MB-231 cells more efficiently. The prodrug was synthesized by solid-phase peptide synthesis method and examined as a substrate of pure prolidase as well as cell homogenate. The cytotoxicity against MDA-MB-231 and non-methotrexate resistant breast cancer cell line, MCF-7 was also examined by XTT assay. The results showed that Pro-MTX was a substrate of prolidase. It was also shown that the prodrug could be converted to parent drug methotrexate in Caco-2 and HeLa cell homogenate. When tested with Caco-2 and MCF-7 cells, Pro-MTX showed weaker cytotoxicity compared with methotrexate. But for methotrexate resistant MDA-MB-231 cells, Pro-MTX showed stronger activity than methotrexate. The results indicated that the proline prodrug of methotrexate may overcome the resistance of human breast cancer cells in culture. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.024