title: Structure-activity relationships of saframycins.
abstract: In vitro antitumor activities of 13 saframycins, including the potent antitumor component, saframycin A, were determined with the highly sensitive established cell line of L1210 mouse leukemia to investigate structure-activity relationships. Saframycins which lack the alpha-cyanoamine group or the alpha-carbinolamine group exhibited much lower cytotoxic activity than saframycin A. The modification of active saframycins either at the C-14 position on the basic skeleton or at the C-25 position on the side chain with bulky substituents resulted in a decrease in cytotoxic activity. These structure-activity relationships corroborated the proposed major mechanism of action for the antitumor activity of saframycin A and supported our proposed model for the saframycin A-DNA adduct.
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic; D002460:Cell Line; D007546:Isoquinolines / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines