Synthesis and cytotoxic activity of 7-oxo-7H-dibenz[f,ij]isoquinoline and 7-oxo-7H-benzo[e]perimidine derivatives.
A series of 7-oxo-7H-dibenz[f,ij]isoquinoline and 7-oxo-7H-benzo[e]perimidines bearing cationic side chains were prepared from aminoanthraquinones. The perimidines were prepared from 1-aminoanthraquinone by initial condensation with urea or dimethylacetamide. A series of 2-, 4-, 8-, and 11-carboxy derivatives of the dibenzisoquinolines were prepared from aminoanthraquinonecarboxylic acids. The cationic derivatives were prepared from these via amide, amine, or methylene linkers to study the effects of side chain positioning on biological activity. Within the series of carboxamide-linked compounds, the order of increasing cytotoxicity was 8- < 4- < 2- < 11-. The 2- and 4-carboxamides showed substantial growth delays against in vivo subcutaneous colon 38 tumors in mice, but the 11-carboxamide had curative activity in this refractory model and is being investigated further.
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Chemistry Department, La Trobe University, Bundoora, Victoria 3083, Australia.
Deady
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LW
Finlay
G J
GJ
Baguley
B C
BC
Denny
W A
WA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000633:toxicity; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D019169:Jurkat Cells; D007941:Leukemia P388; D008175:Lung Neoplasms; D051379:Mice; D008815:Mice, Inbred Strains; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D007546:Isoquinolines; D011799:Quinazolines; D004317:Doxorubicin