MedKoo Biosciences/Dactinomycin/100220/2g

Synonym:Abbreviation:DACT;ACTD;actinomycinC1;actinomycinD;actinomycinI1;actinomycinIV;actinomycinX1;actinomycinthrvalprosarmeval;dactinomycine;meractinomycin;USbrandnames:Cosmegen;Lyovac.

IUPAC/ChemicalName:2-amino-N1,N9-bis((6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1]oxa[4,7,10,13]tetraazacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide

InChiKey:RJURFGZVJUQBHK-IIXSONLDSA-N

InChiCode:InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1

SMILESCode:O=C(N[C@@H]1C(N[C@@H](C(N2[C@]([H])(C(N(CC(N([C@H](C(O[C@@H]1C)=O)C(C)C)C)=O)C)=O)CCC2)=O)C(C)C)=O)C3=C(C(C(C)=C4OC5=C(C(C(N[C@@H]([C@@H](C)O6)C(N[C@H](C(C)C)C(N7CCC[C@@]7([H])C(N(C)CC(N(C)[C@@H](C(C)C)C6=O)=O)=O)=O)=O)=O)=CC=C5C)N=C43)=O)N

TechnicalData

AdditionalInformation

DactinomycinisachromopeptideantineoplasticantibioticisolatedfromthebacteriumStreptomycesparvulus.Dactinomycinintercalatesbetweenadjacentguanine-cytosinebasepairs,blockingthetranscriptionofDNAbyRNApolymerase;italsocausessingle-strandDNAbreaks,possiblyviaafree-radicalintermediateoraninteractionwithtopoisomeraseII.Checkforactiveclinicaltrialsorclosedclinicaltrialsusingthisagent.(NCIThesaurus).
  
Clinicaluse
Aschemotherapy: ActinomycinD,marketedunderthetradenameDactinomycin,isoneoftheolderchemotherapydrugs,andhasbeenusedintherapyformanyyears.Itisaclear,yellowliquidadministeredintravenouslyandmostcommonlyusedintreatmentofavarietyofcancersincludinggestationaltrophoblasticneoplasia, Wilms'tumorandrhabdomyosarcoma.
 
 Asanantibiotic:Itwasthefirstantibioticshowntohaveanti-canceractivity,butisnotnormallyusedassuch,asitishighlytoxic,causingdamagetogeneticmaterial.
 
Researchuse:ActinomycinDanditsfluorescentderivative,7-aminoactinomycinD(7-AAD),areusedasstainsinmicroscopyandflowcytometryapplications.Theaffinityofthesestains/compoundsforGC-richregionsofDNAstrandsmakesthemexcellentMarkersforDNA.7-AADbindstosinglestrandedDNA;thereforeitisausefultoolindeterminingapoptosisanddistinguishingbetweendeadcellsandliveones.Fromhttp://en.wikipedia.org/wiki/Dactinomycin.
 
DRUGDESCRIPTION
Dactinomycinisoneoftheactinomycins,agroupofantibioticsproducedbyvariousspeciesofStreptomyces.DactinomycinistheprincipalcomponentofthemixtureofactinomycinsproducedbyStreptomycesparvullus.UnlikeotherspeciesofStreptomyces,thisorganismyieldsanessentiallypuresubstancethatcontainsonlytracesofsimilarcompoundsdifferingintheaminoacidcontentofthepeptidesidechains.TheempiricalformulaisC62H86N12O16.COSMEGENisasterile,yellowtoorangelyophilizedpowderforinjectionbytheintravenousrouteorbyregionalperfusionafterreconstitution.Eachvialcontains0.5mg(500mcg)ofdactinomycinand20.0mgofmannitol.
 
MechanismofAction
Generally,theactinomycinsexertaninhibitoryeffectongram-positiveandgram-negativebacteriaandonsomefungi.However,thetoxicpropertiesoftheactinomycins(includingdactinomycin)inrelationtoantibacterialactivityaresuchastoprecludetheiruseasantibioticsinthetreatmentofinfectiousdiseases.Becausetheactinomycinsarecytotoxic,theyhaveanantineoplasticeffectwhichhasbeendemonstratedinexperimentalanimalswithvarioustypesoftumorimplants.Thiscytotoxicactionisthebasisfortheiruseinthetreatmentofcertaintypesofcancer.DactinomycinisbelievedtoproduceitscytotoxiceffectsbybindingDNAandinhibitingRNAsynthesis.
 
 

References

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