Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of camptothecin
Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of camptothecin
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DOI：
10.1016/s0960-894x(00)00649-1
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发表时间：
2001-02-12
影响因子：
2.7
通讯作者：
Zunino, F
中科院分区：
文献类型：
--
作者：
Dallavalle, S;Ferrari, A;Zunino, F
以喜树碱-7-醛和喜树碱的芳环为原料，合成了一系列新的喜树碱-7-亚氨甲基衍生物。脂环族和脂肪族胺，它们的氢化导致相应的胺。与拓扑替康相比，所有亚胺和极性较小的胺对H460非小细胞肺癌细胞系的细胞毒活性均显示出显著增加。喜树碱7位取代基的亲脂性对细胞毒效力起重要作用。7-苯基-亚氨基甲基衍生物在体内对无胸腺裸鼠中异种移植的NSCLC H460显示出与托泊替康相当的功效。(C)2001爱思唯尔科技有限公司版权所有。
A series of new 7-iminomethyl derivatives of camptothecin were obtained from camptothrein-7-aldehyde and aromatic. alicyclic and aliphatic amines, Their hydrogenation led to the corresponding amines. All the imines and the less polar amines showed a marked increase of the cytotoxic activity against H460 non-small lung carcinoma cell line with respect to topotecan. The lipophilicity of the substituent in position 7 of camptothecin stems to play an important role for cytotoxic potency. The 7-phenyl-iminomethyl derivative showed efficacy comparable to topotecan in vivo against NSCLC H460 xenografted in athymic nude mice. (C) 2001 Elsevier Science Ltd. All rights reserved.