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对联三苯类拓扑异构酶抑制剂的合成及抗肿瘤活性研究.docx

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对联三苯类拓扑异构酶抑制剂的合成及抗肿瘤活性研究 Abstract Topoisomeraseinhibitorsareanimportantclassofantitumordrugs.Inthisstudy,wesynthesizedaseriesoftopoisomeraseinhibitorsbasedontriphenylcompoundswithdifferenttopologicalisomersandevaluatedtheirantitumoractivityusingMTTassay.Theresultsshowedthatsomeofthecompoundsdemonstratedpotentinhibitionagainstcancercelllinesandmayhavepotentialasantitumoragents. Introduction TopoisomerasesareenzymesresponsibleforthemaintenanceofDNAtopologyduringreplication,transcription,andchromosomalcondensation.Theyareessentialfortheproperfunctionofthecellandtheirinhibitioncanleadtocelldeath.Topoisomeraseinhibitorsareaclassofantitumordrugsthatpreventtheenzymefromcompletingitsfunction,leadingtoDNAdamageandapoptosis.Themostwidelystudiedtopoisomeraseinhibitorsareanthracyclines,camptothecins,andepipodophyllotoxins.However,theirclinicaluseislimitedduetodrugresistance,toxicity,andotherfactors.Therefore,thereisaneedtodevelopnewtopoisomeraseinhibitorsthataremoreeffectiveandsafer. Triphenylcompoundsareaclassofcompoundsthathavebeenshowntobeeffectiveininhibitingtopoisomerases.Theycontainthreephenylgroupsconnectedbydifferentlinkers,resultingindifferenttopologicalisomers.Thedifferentisomershavebeenshowntohavedifferentbiologicalactivities.Forexample,thepropeller-shapedisomerismoreeffectiveininhibitingtopoisomeraseIIthanthebowl-shapedisomer.Therefore,wesynthesizedaseriesoftriphenylcompoundswithdifferenttopologicalisomersandevaluatedtheirantitumoractivity. MaterialsandMethods Chemicals Allchemicalsusedwereofanalyticalgrade.ThestartingmaterialswerepurchasedfromSigma-Aldrich. Synthesisoftriphenylcompounds Thetriphenylcompoundsweresynthesizedusingapreviouslyreportedmethodwithsomemodifications.Briefly,thestartingmaterialswererefluxedinthepresenceofastrongacidcatalysttoformthedesiredtriphenylcompounds.ThereactionwasmonitoredbyTLCandthecrudeproductwaspurifiedbycolumnchromatography. CellcultureandMTTassay Humancancercelllines(HeLa,MCF-7,andA549)wereobtainedfromtheAmericanTypeCultureCollec