Amsacrine
{{Short description|Chemical compound}}
{{drugbox
| verifiedrevid = 457129529
| IUPAC_name = N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide
| image = Amsacrine.svg
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 00DPD30SOY
| smiles = O=S(=O)(Nc1ccc(c(OC)c1)Nc2c4c(nc3c2cccc3)cccc4)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XCPGHVQEEXUHNC-UHFFFAOYSA-N
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 51264-14-3
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 43
| ATC_prefix = L01
| ATC_suffix = XX01
| ATC_supplemental =
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 2687
| PubChem = 2179
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2094
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00276
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02321
| C=21 | H=19
| N=3 | O=3
| S=1
| bioavailability =
| protein_bound = 96 to 98%
| metabolism =
| elimination_half-life = 8–9 hours
| excretion =
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category =
| legal_AU =
| legal_UK =
| legal_US = a
| legal_status =
| routes_of_administration =
}}
Amsacrine (synonyms: m-AMSA, acridinyl anisidide) is an antineoplastic agent.
It has been used in acute lymphoblastic leukemia.{{cite journal | vauthors = Horstmann MA, Hassenpflug WA, zur Stadt U, Escherich G, Janka G, Kabisch H | title = Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in children | journal = Haematologica | volume = 90 | issue = 12 | pages = 1701–3 | date = December 2005 | pmid = 16330449 }}
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.{{cite journal | vauthors = Ketron AC, Denny WA, Graves DE, Osheroff N | title = Amsacrine as a Topoisomerase II Poison: Importance of Drug-DNA Interactions | journal = Biochemistry | volume = 51 | issue = 8 | pages = 1730–1739 | date = February 2012 | pmid = 22304499 | doi = 10.1021/bi201159b | pmc = 3289736 }} 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.{{cite journal | vauthors = Wadkins RM, Graves DE | title = Thermodynamics of the interactions of m-AMSA and o-AMSA with nucleic acids: influence of ionic strength and DNA base composition | journal = Nucleic Acids Research | volume = 17 | issue = 23 | pages = 9933–46 | date = December 1989 | pmid = 2602146 | pmc = 335223 | doi = 10.1093/nar/17.23.9933 }}{{cite journal | vauthors = DeMarini DM, Doerr CL, Meyer MK, Brock KH, Hozier J, Moore MM | title = Mutagenicity of m-AMSA and o-AMSA in mammalian cells due to clastogenic mechanism: possible role of topoisomerase | journal = Mutagenesis | volume = 2 | issue = 5 | pages = 349–55 | date = September 1987 | pmid = 2830452 | doi = 10.1093/mutage/2.5.349 }}{{cite journal | vauthors = Nitiss JL | title = Targeting DNA topoisomerase II in cancer chemotherapy | journal = Nature Reviews. Cancer | volume = 9 | issue = 5 | pages = 338–50 | date = May 2009 | pmid = 19377506 | pmc = 2748742 | doi = 10.1038/nrc2607 }}
References
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{{Chemotherapeutic agents}}
Category:IARC Group 2B carcinogens
Category:Topoisomerase inhibitors
{{antineoplastic-drug-stub}}