Novel cytotoxic 7-iminomethyl and 7-aminomethyl derivatives of camptothecin.
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.
Dallavalle
S
S
Dipartimento di Scienze Molecolari Agroalimentari, Sezione di Chimica, Università di Milano, Italy.
Ferrari
A
A
Merlini
L
L
Penco
S
S
Carenini
N
N
De Cesare
M
M
Perego
P
P
Pratesi
G
G
Zunino
F
F
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin