Amsacrine

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Amsacrine
Amsacrine.svg
Clinical data
ATC code
Legal status
Legal status
  • US:a
Pharmacokinetic data
Protein binding 96 to 98%
Elimination half-life 8–9 hours
Identifiers
  • N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.051.887 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C21H19N3O3S
Molar mass 393.46 g·mol−1
3D model (JSmol)
  • O=S(=O)(Nc1ccc(c(OC)c1)Nc2c4c(nc3c2cccc3)cccc4)C
  • InChI=1S/C21H19N3O3S/c1-27-20-13-14(24-28(2,25)26)11-12-19(20)23-21-15-7-3-5-9-17(15)22-18-10-6-4-8-16(18)21/h3-13,24H,1-2H3,(H,22,23) Yes check.svgY
  • Key:XCPGHVQEEXUHNC-UHFFFAOYSA-N Yes check.svgY
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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, which differs only in the position of the methoxy substituent on the anilino ring, exhibits limited ability to poison topoisomerase II despite its intercalative properties. This suggests that intercalation alone is insufficient to stabilize topoisomerase II as a covalent complex on DNA. [3] [4] [5]

References

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