title: Potential antitumor agents. 37. Organophosphorus derivatives of 9-anilinoacridine.
abstract: A series of 9-anilinoacridine derivatives substituted in the anilino ring with a variety of phosphoramide and related substitutents has been prepared, and the antitumor activity has been evaluated both in vivo and in vitro against the L1210 or P-388 mouse leukemia systems. The DNA-binding properties were measured using the ethidium displacement method, and the structural requirements for strong binding were found to differ from those for antileukemic activity. For high biological activity a marked preference for oxygen-containing substituents on the phosphorus atom was noted, while for high DNA binding a requirement for nitrogen-containing or cyclized substituents was observed. The most active congeners, as assayed in both in vitro and in vivo systems, were comparable in activity to the clinically utilized anilinoacridine derivative N-[4'-(9-acridinylamino)-3'-methoxyphenyl]methanesulfonamide (m-AMSA, amsacrine).
mesh_terms: D000609:Aminoacridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
chemical_list: D000609:Aminoacridines; D000970:Antineoplastic Agents; D004247:DNA