title: Potential antitumor agents. 50. In vivo solid-tumor activity of derivatives of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide.
abstract: The synthesis, physicochemical properties, and antitumor activity of a series of N-[2-(dialkylamino)alkyl]-acridine-4-carboxamides are reported. The compounds bind to DNA by intercalation, but exist under physiological conditions as monocations due to the weakly basic acridine chromophore (pKa = 3.5-4.5). The acridine-4-carboxamides show very broad structure-activity relationships (SAR) for antileukemic activity, with substituents at nearly all acridine positions proving acceptable. The compounds also show remarkable activity against the Lewis lung solid tumor in vivo, with several analogues capable of effecting 100% cures of the advanced disease. The broad SAR and high solid-tumor activity of the 9-acridine-4-carboxamides imply they should be considered as a completely new class of antitumor agent.
mesh_terms: D000609:Aminoacridines / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use*; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D013329:Structure-Activity Relationship
chemical_list: D000609:Aminoacridines; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D004247:DNA