Amsacrine Explained

Amsacrine (synonyms: m-AMSA, acridinyl anisidide) is an antineoplastic agent.

It has been used in acute lymphoblastic leukemia.^[1]

Mechanism

Its planar fused ring system can intercalate into the DNA of tumor cells, thereby altering the major and minor groove proportions. These alterations to DNA structure inhibit both DNA replication and transcription by reducing association between the affected DNA and: DNA polymerase, RNA polymerase and transcription factors.

Amsacrine also expresses topoisomerase inhibitor activity, specifically inhibiting topoisomerase II.^[2] In contrast, the structurally similar o-AMSA differing in the position of the methoxy substituent group on the anilino-ring have little ability to poison topoisomerase II despite its intercalative behavior, suggesting that intercalation of the molecule in itself is insufficient to trap topoisomerase II as a covalent complex on DNA.^{[3] [4] [5]}

Notes and References

1. Horstmann MA, Hassenpflug WA, zur Stadt U, Escherich G, Janka G, Kabisch H . Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in children . Haematologica . 90 . 12 . 1701–3 . December 2005 . 16330449 .
2. Ketron AC, Denny WA, Graves DE, Osheroff N . Amsacrine as a Topoisomerase II Poison: Importance of Drug-DNA Interactions . Biochemistry . 51 . 8 . 1730–1739 . February 2012 . 22304499 . 10.1021/bi201159b . 3289736 .
3. Wadkins RM, Graves DE . Thermodynamics of the interactions of m-AMSA and o-AMSA with nucleic acids: influence of ionic strength and DNA base composition . Nucleic Acids Research . 17 . 23 . 9933–46 . December 1989 . 2602146 . 335223 . 10.1093/nar/17.23.9933 .
4. DeMarini DM, Doerr CL, Meyer MK, Brock KH, Hozier J, Moore MM . Mutagenicity of m-AMSA and o-AMSA in mammalian cells due to clastogenic mechanism: possible role of topoisomerase . Mutagenesis . 2 . 5 . 349–55 . September 1987 . 2830452 . 10.1093/mutage/2.5.349 .
5. Nitiss JL . Targeting DNA topoisomerase II in cancer chemotherapy . Nature Reviews. Cancer . 9 . 5 . 338–50 . May 2009 . 19377506 . 2748742 . 10.1038/nrc2607 .