Antineoplastic agents. Structure-activity relationship study of bis(substituted aminoalkylamino)anthraquinones.

A structure-activity relationship study was conducted on a number of bis(substituted aminoalkylamino)anthraquinones. These compounds were prepared by the condensation of substituted or unsubstituted leucoquinizarin with appropriate amines, followed by air oxidation. Both the position and the nature of the center nitrogen atom of the side chain are vital to the antineoplastic activity. The possible mode of action of these aminoquinones was discussed. 1,4-Dihydroxy-5,8-bis[[2-(hydroxyethyl)amino]ethyl]amino-9,10-anthracenedione (DHAQ) was found to possess potent inhibitory activity against both the P-388 leukemia system (T/C of 299 at 0.5 mg/kg with 4/6 cures) and the B-16 melanoma system (T/C of 503 at 1 mg/kg with 7/10 cures).