马拉巴酮C的大鼠肝微粒体生物转化及其体外对人胃癌细胞株的细胞毒活性研究.pdf

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1、JournalofChinesePharmaceuticalScienceshttp：／1www．jcps．ac．cn24lBiotransformationofmalabaric0neCbyrathepaticmicrosomesandcytotoxicactivitiesagainstgastriccancercellsinvitroNiWu，WeiXu，YouboZhang，XiuweiYangStateKeyLaboratoryofNaturalandBiomimeticDrugs,"DepartmentofNaturalMe

2、dicines；SchoolofPharmaceuticalSciencesPekingUniversityHealthScienceCenter,Beo'ing100191，ChinaAbstract：MalabariconeCfl1，isolatedfromtheseedsofMyristicafragransHoutt．，belongstoakindofdiarylnonanoidcompoundsthatareonlyfoundinMyristicaceaetillnow．Inthisstudy．biotransformati

3、onof1wasinvestigatedusingrathepaticmicrosomesforthefirsttimeandthemainbiotransformationproductwaselucidatedasmalabariconeB(2)accordingtothespectroscopicdata．Furtherevaluationonhumangastriccancereel1linesshowedthatthecytotoxiceffectsofmalabariconeCanditsmetabolitemalabar

4、iconeBwerecomparabletothoseofvinorelbine，withthevaluesofIC50of(42．62~3．10)and(19．80-4-1．70)~tg／mLonNCI．N87．and(22．94~1．33)and(19．60~2．21)gg／mLonMGC803，respectively．StatisticalanalysisrevealedthatmalabariconeBhadsignificantlystrongercytotoxicitythantheparentcompound(尸<0．

5、01onNCI—N87andP<0．05onMGC803)，whichmayindicateabioactivationofmalabariconeCbyhepaticmicrosomes．TheseresultssuggestthatmalabariconeChasasimplebiotransformationpathwaybyhepaticmicrosomesandprovidevaluableinformationforfurtherinvestigationonboththeparentcompoundanditsbiotr

6、ansformationproductasanti—gastriccanceragentsorleadcompounds．Keywords：MalabariconeC：MalabariconeB：Myristicafragrans；Biotransformation；Rathepaticmicrosomes；HumangastriccancerNCI．N87；HumangastriccancerMGC803CLCnumber：R284Documentcode：AArticleID：1003—1057(2014)4_241—051．In

7、tr0ductiOnimportantstepsindrugdevelopment，whichcanaffecttheoveralltherapeuticandtoxicprofiles．Nutmeg，theseedofMyristicafragransHoutt．(Family：GastriccancerisoneoftheleadingtypesofcancerMyristicaceae)．isoneofthemostwidelyusedspicesworldwide[15Jandawel1．knowntraditionalChi

8、nesemedicinesfTCM)．Withthefactthatpresenttherapiesshowlimitedsuccess，developingnew，activedrugsagainstforthetre