新型有机硒化合物的合成及其抗癌活性的分析-synthesis of novel organic selenium compounds and analysis of their anticancer activities.docxVIP

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新型有机硒化合物的合成及其抗癌活性的分析-synthesis of novel organic selenium compounds and analysis of their anticancer activities.docx

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新型有机硒化合物的合成及其抗癌活性的分析-synthesis of novel organic selenium compounds and analysis of their anticancer activities

AbstractSeleniumisoneoftheessentialtraceelementsinhumanbody,whichiscloselyrelatedtomaintainandcontinuethehumanlife.Inthehumanbody,Seleniumismainlyexistsintheformofseleniumprotease,forexample:glutathioneperoxidase.Ebselenhasattractedmuchattentionbecauseofitsanti-inflammatory,antioxidantandantitumoractivity.AndthestudyhasfoundthatthephysiologicalactivityofebselenissimilartotheGSH-Px.1,3,4-Thi-adiazolederivativesthathaveantibacterial,antiviral,antitumoractivityandotherbiologicalactivity,hasbeenwidelyusedinagricultureandmedicineresearchandapplication.Basedonthis,weusedtheebselenasleadcompound,designedandsynthesizednewsixteenorganicseleniumcompoundswhichdidnotreportedinliteratures.WehaveconfirmedthestructuresofthesecompoundsbyIR,1HNMRandESI-MSandelementalanalysismethods,andevaluatedfortheircytotoxicityinvitro-againsthumancancercellsA549,SMMC-7721andMCF-7byCCK-8assay.ForA549cells,allcompoundsshowedhigheractivitiesthanpositivecontrol5-fluorouracil.Whereas,mostofthemdisplayedlowerantitumoractivitiesthanethaselen.Withtheexceptionofcompound8a,theothercompoundswhichcarringvarioussubstituentsalldisplayedincreasedactivitiesincomparisontocompound8a.TheseresultssuggestthatthepresenceofsubstituentgroupsatthephenylringisfavorableforimprovingthepotencyofcompoundsagainstA549cells.ForSMMC-7721cells,mostofthenewlysynthesizedcompoundsexhibitedverygoodantitumoractivitiesagainstSMMC-7721cells.Especiallythecompound8gwhichbearing4-methoxysubstituentatthephenylringdisplayedverygoodantiproliferativeeffectswithIC50valueof2.08μmol/L.Exceptthecompoundsof8land8pwhichdisplayedmoderateantitumoractivities,theothercompoundsdisplayedhigheractivitiesthanpositivecontrolethaselen.ForMCF-7cells,allcompoundsshowedmuchbetterpotencythanpositivecontrolethaselen.Meanwhile,exceptthecompoundsof8d,8land8nexhibitedmoderateantitumoractivity,theothercompoundsdisplayedverygoodantiproliferativeeffectswithinIC50values6.04μmol/L.Compounds8band8mhavedisplayedhighlyeffectivebiologicalactivitiesagainstMCF-7cellswithIC50valu