Aurora-B激酶抑制剂的合成及其生物活性研究的开题报告-第一文库 | 海量文档资源下载与分享平台

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AuroraB激酶抑制剂的合成及其生物活性研究的开题报告Title:SynthesisandBiologicalActivityEvaluationofAuroraBKinaseInhibitorsIntroduction:AuroraBkinaseisacrucialregulatorofmitosisandhasbeenimplicatedintumorigenesisandcancerprogression.Therefore,itisanattractivetargetforthedevelopmentofanticancerdrugs.Inrecentyears,anumberofsmallmoleculeinhibitorsofAuroraBkinasehavebeendeveloped,butmanyofthemsufferfrompoorpharmacokineticpropertiesandlimitedefficacy.Therefore,thereisaneedforthedevelopmentofnewagentswithimprovedefficacyandsafetyprofiles.Objectives:TheobjectivesofthisstudyaretosynthesizeaseriesofAuroraBkinaseinhibitorsusingacomputational-guideddesignapproach,andtoevaluatetheirbiologicalactivityinvitroandinvivo.Methods:Acomputational-guideddesignapproachwillbeusedtodesigntheAuroraBkinaseinhibitors.Thecompoundswillbesynthesizedusingstandardorganicsynthesistechniquessuchasnucleophilicsubstitution,Suzukicoupling,andSonogashiracoupling.ThepurityandstructureofthesynthesizedcompoundswillbeconfirmedusingNMRandmassspectrometry.TheAuroraBkinaseinhibitoryactivityofthecompoundswillbeevaluatedusinganinvitrokinaseassay.Themostpromisingcompoundswillbefurtherevaluatedincell-basedassaystoassesstheirantiproliferativeactivityagainstcancercells.Theselectivityandtoxicityofthecompoundswillalsobeevaluated.ExpectedResults:WeexpecttosynthesizeaseriesofpotentandselectiveAuroraBkinaseinhibitors.Thecompoundswillbecharacterizedbytheirchemicalstructuresandpurity.TheinvitrokinaseassayresultswillprovideinformationontheinhibitoryactivityofthecompoundsagainstAuroraBkinase.Thecell-basedassayswillprovideinformationontheantiproliferativeactivityofthecompoundsandtheirselectivity.Iftheresultsarepromising,wewillfurtherevaluatetheefficacyandtoxicityofthemostpromisingcompoundinvivousinganimalmodels.Conclusion:ThedevelopmentofnovelAuroraBkinaseinhibitorswithimprovedsafetyandefficacyprofilesisofgreatimportanceincancerresearch.ThisstudyaimstosynthesizeaseriesofAuroraBkinaseinhibitorsandevaluatetheiractivityinvitroandinvivo.Ifthe