Dallavalle S, Ferrari A, Merlini L, Penco S, Carenini N, De Cesare M, Perego P, Pratesi G, Zunino F
Dipartimento di Scienze Molecolari Agroalimentari, Sezione di Chimica, Università di Milano, Italy.
Bioorg Med Chem Lett. 2001 Feb 12;11(3):291-4. doi: 10.1016/s0960-894x(00)00649-1.
A series of new 7-iminomethyl derivatives of camptothecin were obtained from camptothecin-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 seems to play an important role for cytotoxic potency. The 7-phenyliminomethyl derivative showed efficacy comparable to topotecan in vivo against NSCLC H460 xenografted in athymic nude mice.
从喜树碱 -7-醛与芳香胺、脂环胺和脂肪胺反应得到了一系列新型喜树碱7-亚胺甲基衍生物。它们经氢化反应生成相应的胺。与拓扑替康相比，所有的亚胺和极性较小的胺对H460非小细胞肺癌细胞系的细胞毒性活性均显著增强。喜树碱7位取代基的亲脂性似乎对细胞毒性效力起着重要作用。7-苯基亚胺甲基衍生物在体内对无胸腺裸鼠移植的NSCLC H460的疗效与拓扑替康相当。
