Amsacrine

Amsacrine
Clinical data
ATC code	L01XX01 (WHO) ;
Legal status
Legal status	US: a ;
Pharmacokinetic data
Protein binding	96 to 98%
Elimination half-life	8–9 hours
Identifiers
	IUPAC name N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide;
CAS Number	51264-14-3 ;
PubChem CID	2179;
DrugBank	DB00276 ;
ChemSpider	2094 ;
UNII	00DPD30SOY;
KEGG	D02321 ;
ChEBI	CHEBI:2687 ;
ChEMBL	ChEMBL43 ;
CompTox Dashboard (EPA)	DTXSID4022604 ;
ECHA InfoCard	100.051.887
Chemical and physical data
Formula	C21H19N3O3S
Molar mass	393.46 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=S(=O)(Nc1ccc(c(OC)c1)Nc2c4c(nc3c2cccc3)cccc4)C;
	InChI 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) ; Key:XCPGHVQEEXUHNC-UHFFFAOYSA-N ;
	(verify)

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]

References

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.
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. PMID 22304499.
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.
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.
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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[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. 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.