Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of camptothecin

A series of new 7-iminomethyl derivatives of camptothecin were obtained fro m camptothrein-7-aldehyde and aromatic. alicyclic and aliphatic amines, The ir hydrogenation led to the corresponding amines. All the imines and the le ss polar amines showed a marked increase of the cytotoxic activity against H460 non-small lung carcinoma cell line with respect to topotecan. The lipo philicity 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 xenograf ted in athymic nude mice. (C) 2001 Elsevier Science Ltd. All rights reserve d.