Papot S, Combaud D, Bosslet K, Gerken M, Czech J, Gesson J P
Laboratoire de Synthèse et Réactivité des Substances naturelles, Université de Poitiers et CNRS, France.
Bioorg Med Chem Lett. 2000 Aug 21;10(16):1835-7. doi: 10.1016/s0960-894x(00)00353-x.
A new glucuronylated prodrug of nornitrogen mustard, incorporating the same spacer group as the doxorubicin prodrug HMR 1826, has been prepared. Upon exposure to E. coli beta-glucuronidase, fast hydrolysis occurs but a lower cytotoxicity against LoVo cancer cells is observed compared to the nornitrogen mustard alone. This is explained by cyclization of the intermediate carbamic acid to the inactive chloroethyl oxazolidinone.
已制备出一种去甲氮芥的新型葡糖醛酸化前药，其包含与阿霉素前药HMR 1826相同的间隔基团。在暴露于大肠杆菌β-葡糖醛酸酶时，会快速发生水解，但与单独的去甲氮芥相比，观察到对LoVo癌细胞的细胞毒性较低。这是由于中间氨基甲酸环化形成无活性的氯乙恶唑烷酮所致。
