Aurora B激酶抑制剂的合成及其生物活性研究的开题报告.docx

AuroraB激酶抑制剂的合成及其生物活性研究的开题报告

Title:SynthesisandBiologicalActivityEvaluationofAuroraBKinaseInhibitors

Introduction:

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,wewillfurtherevaluatetheefficacyandtoxici