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] perimi dines bearing cationic side chains were prepared from aminoanthraquinones. The perimidines were prepared from 1-aminoanthraquinone by initial condensa tion with urea or dimethylacetamide. A series of 2-, 4-, 8-, and 11-carboxy derivatives of the dibenzisoquinolines were prepared from aminoan-thraquin onecarboxylic acids. The cationic derivatives were prepared from these via amide, amine, or methylene linkers to study the effects of side chain posit ioning on biological activity. Within the series of carboxamide-linked comp ounds, the order of increasing cytotoxicity was 8- < 4- < 2- < 11-. The 2- and 4-carboxamides showed substantial growth delays against in vivo subcuta neous colon 38 tumors in mice, but the 11-carboxamide had curative activity in this refractory model and is being investigated further.