title: Chromophore-modified antineoplastic imidazoacridinones. Synthesis and activity against murine leukemias.
abstract: The synthesis of 8-hydroxy and 8-methoxy analogues of some substituted 5-aminoimidazoacridinones (4) is described. The synthesis was carried out by a three-step sequence from the corresponding 1-chloro-4-nitro-9(10H)-acridinone precursors (1). The annulation of the imidazolo ring onto the aminoacridinone chromophore was accomplished by heating the required aminoacridinone (3) with formic acid or, in the case of 1-methyl derivatives, with N,N-dimethylacetamide. Potent cytotoxic activity against L1210 leukemia, as well as antitumor activity against P388 leukemia in mice, was demonstrated for the 8-hydroxy analogues. The corresponding 8-methoxy derivatives were not cytotoxic. However, in some cases, they showed significant in vivo antileukemic activity.
authors.affiliation: Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland.
authors.forename: W M
authors.initials: WM
authors.lastname: Cholody
authors.forename: S
authors.initials: S
authors.lastname: Martelli
authors.forename: J
authors.initials: J
authors.lastname: Konopa
mesh_terms: D000609:Aminoacridines / Q000138:chemical synthesis* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D007093:Imidazoles / Q000138:chemical synthesis / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000609:Aminoacridines; D000970:Antineoplastic Agents; D007093:Imidazoles