Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity.
Replacement of the 3'-methoxy group of the clinical antileukemic agent amsacrine with a 3'-methylamino group provides a compound (3) with a broader spectrum of action, including in vivo activity against experimental solid tumors. The synthesis, physicochemical properties, and biological activity of a series of acridine-substituted analogues of 3 are described. The compounds show higher levels of DNA binding, water solubility, and in vivo solid tumor activity (lewis lung carcinoma) than their amsacrine counterparts. However, the structure-activity relationships for acridine substitution are different, with 3,5-disubstituted 3'-methylamino compounds showing the highest activity (compared to 4,5-disubstituted amsacrine analogues).
D000166:Acridines; D000609:Aminoacridines / Q000378:metabolism / Q000627:therapeutic use*; D000677:Amsacrine; D000818:Animals; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy; D004247:DNA / Q000378:metabolism; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D012995:Solubility; D013329:Structure-Activity Relationship
D000166:Acridines; D000609:Aminoacridines; D000677:Amsacrine; D004247:DNA