Potential Antitumor Agents. 48. 3'-Dimethylamino Derivatives of Amsacrine: Redox Chemistry and in Vivo Tumor Activity

Article abstract of DOI:10.1021/jm00387a012

Structure-activity relationships for a series of acridine-substituted 3'-N(CH3)2 derivatives of the clinical antileukemic drug amsacrine (1) are reported.The parent (unsubstituted) compound 3 has activity against the Lewis lung solid tumor that is superior to amsacrine(1), the new clinical amsacrine analogue 4, and the recently developed 3'-NHCH3 derivative 2.Although the compounds generally bind less well to DNA and are less dose potent in vivo than either their amsacrine (3'-OCH3) or 3'-NHCH3 analogues, they show very high levels of antitumor activity, with the 4-OCH3 derivative capable of effecting 100percent cures of the Lewis lung solid tumor.The broad structure-activity relationships for acridine substitution more closely resemble those of the amsacrine than the 3'-NHCH3 series, with 4-substituted and 4,5-disubstituted compounds showing the highest activity.