DNA-synthesis and tumor growth inhibitions by AGGA, a bleomycin-amsacrine hybrid derivative.
AGGA, [[(amino-2-ethyl)-2-aminomethyl]-2-pyridine-6-carboxylhistidyl-ami no-4- butyrylglycylamino]-4-phenyl-1-amino-9-acridine is a synthetic model gathering the simplified metal-chelating part of bleomycin and the intercalating moiety of amsacrine. This molecule was found to possess the metal-complexing and intercalative properties of both antitumor parent drugs. On the basis of results obtained on L1210 and HeLa S3 cells growth inhibition studies and labeled thymidine assay, AGGA clearly indicates a cytostatic activity. On the other hand, the oxygenated free radicals produced in the presence of iron and oxygen do not seem to be able to cleave DNA as BLM does. This lack of cytotoxicity is analyzed in terms of fundamental differences between BLM and AGGA-DNA complexes.
D000609:Aminoacridines / Q000494:pharmacology*; D000677:Amsacrine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000378:metabolism*; D006878:Hydroxides; D017665:Hydroxyl Radical; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000609:Aminoacridines; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006878:Hydroxides; D000677:Amsacrine; C055380:(N-(2-((4-((2-((4-(9-acridinylamino)phenyl)amino)-2-oxoethyl)amino)-4-oxobutyl)amino)-1-(1H-imidazol-4-ylmethyl)-1-oxoethyl)-6-(((-2-aminoethyl)amino)methyl)-2-pyridinecarboxamidato) iron(1+); D001761:Bleomycin; D017665:Hydroxyl Radical