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).

• Authors: G W Rewcastle, B C Baguley, B F Cain
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 25 Issue 10 Pg. 1231-5 (Oct 1982) ISSN: 0022-2623 [Print] United States
• PMID: 7143362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoacridines
• Antineoplastic Agents
• DNA

Topics

• Aminoacridines (chemical synthesis, metabolism, pharmacology)
• Animals
• Antineoplastic Agents (chemical synthesis)
• Chemical Phenomena
• Chemistry
• DNA (metabolism)
• Leukemia L1210 (drug therapy)
• Leukemia P388 (drug therapy)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA