Amsacrine: Difference between revisions

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{{drugbox

| verifiedrevid = ~~443388083~~

| verifiedrevid = 457129529

| IUPAC_name = N-(4-(acridin-9-ylamino)-3-methoxyphenyl)methanesulfonamide

| image = Amsacrine.svg

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 00DPD30SOY

| InChI = 1/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)

| smiles = O=S(=O)(Nc1ccc(c(OC)c1)Nc2c4c(nc3c2cccc3)cccc4)C

| InChIKey = XCPGHVQEEXUHNC-UHFFFAOYAA

⚫

| ~~CASNo_Ref~~ = {{cascite|correct|~~CAS~~}}

| 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}}

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| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D02321

| C=21|H=19|N=3|O=3|S=1

| C=21 | H=19

| N=3 | O=3

| S=1

| molecular_weight = 393.46 g/mol

| bioavailability =

| protein_bound = 96 to 98%

| metabolism =

| elimination_half-life = ~~8-9~~ hours

| elimination_half-life = 8–9 hours

| excretion =

| pregnancy_AU =

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| legal_AU =

| legal_UK =

| legal_US =

| legal_US = a

| legal_status =

| routes_of_administration =

}}

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

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

It has been used in [[acute lymphoblastic leukemia]].<ref>{{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 }}</ref>

It has been used in [[acute lymphoblastic leukemia]].<ref>PMID 16330449</ref>

==Mechanism==

Its planar fused ring system can [[intercalation (~~chemistry~~)|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.

Its planar fused ring system can [[intercalation (biochemistry)|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 ~~(compares~~ ~~with~~ ~~the~~ ~~better~~ ~~known~~ ~~agent~~ ~~[[etoposide]]).<ref>Genetic~~ ~~Response~~ ~~to Metals.~~ ~~Sarkar~~, ~~Bibudhendra.~~ ~~CRC~~ ~~Press,~~ ~~1995~~. ~~ISBN~~ ~~9780824796150~~</ref> 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 of its intercalative behavior, suggesting that intercalation of the molecule in itself is insufficient to trap topoisomerase II as a covalent complex on DNA. <ref>~~PMID~~ 2602146</ref> <ref>~~PMID~~ 2830452</ref> <ref>~~PMID~~ 19377506</ref>

Amsacrine also expresses [[topoisomerase inhibitor]] activity, specifically inhibiting topoisomerase II.<ref>{{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 }}</ref> 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.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref>

==References==

== References ==

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[[Category:IARC Group 2B carcinogens]]

[[Category:Acridines]]

[[Category:~~Phenol~~ ~~ethers~~]]

[[Category:O-methylated phenols]]

[[Category:DNA intercalaters]]

[[Category:Topoisomerase inhibitors]]