Carbonate and carbamate derivatives of 4-demethylpenclomedine as novel anticancer agents.
Carbonate and carbamate derivatives of 4-demethylpenclomedine as novel anticancer agents.
复制标题
4-去甲基戊氯米定的碳酸酯和氨基甲酸酯衍生物作为新型抗癌剂。
DOI：
10.1007/s00280-009-0933-9
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发表时间：
2009
影响因子：
3
通讯作者：
Jursic,BrankoS
中科院分区：
文献类型：
--
作者：
Morgan,LeeRoy;Struck,RobertF;Waud,WilliamR;LeBlanc,Blaise;Rodgers,AndrewH;Jursic,BrankoS
PurposeThe purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients. DM-PEN has been observed to be an active antitumor agent in mouse human xenograft tumor models and non-neurotoxic in a rat model, however, activity in intracranially implanted human glioma xenograft models have not been reported. The major goal was to identify derivatives that are active in brain tumors.MethodsDerivatives were prepared from DM-PEN and evaluated in vivo against human U251 glioblastoma, D54 glioblastoma and MX-1 breast tumor xenografts and mammary tumor 16/C that were implanted in the mammary fat pad or intracranially (IC).ResultsCarbonate and carbamate derivatives were found to be superior to DM-PEN against IC growing human glioblastoma xenografts.ConclusionThe activity of the carbonates and carbamates against human tumor xenografts in vivo suggests consideration of these two series of derivatives of DM-PEN for clinical development.
