植物来源抗肿瘤药物研究进展

,X(,,,400715):,,,;,,,,:;;;;:R286191:A:0253-2670(2007)02-0285-05AdvancesinstudiesonantitumordrugsoriginatedfromplantXIEJun,TANFeng(KeyLaboratoryofEco2environmentsinThreeGorgesReservoirRegion,MinistryofEducation,KeyLaboratoryofPlantEcologyandResourcesinThreeGorgesReservoirRegion,SchoolofLifeSciences,SouthwestUniversity,Chongqing400715,China)Keywords:antitumor;structure2activityrelationship;paclitaxel;camptothecin;vinblastine60,800,600,680,,,,,;;,,1(paclitaxel)1971Wani,(acquiredim2munedeficiencysyndrome,AIDS)Kaposis[1],51%,,111:,,24nm,BN31217231,,,,22nm,,,G2M,[2]112:Ë(1)11211(phenylisoserine):1)22,,,,,[3]2)323)32,4)32,582ChineseTraditionalandHerbalDrugs38220072X:2006207212:863(2002AA212191):(1982),,,Tel:[phone]Fax:[phone]E2mail:[e-mail]3Tel:[phone]Fax:[phone]E2mail:[e-mail]1Fig.1Structureofpaclitaxel,5%5)C2136)C22C23,2S3R2R3S[4]11212Ë(baccatinË):1)C21OH,2)C22O2(O2benzoyl)3)C24O2(O2acyl)4,5,2024)C27,C27,,[5]5)9,6),102;,1027)1028),AC113:(docetax2el,:)(RhonePoulencRorer,RPR),1995,,FDA14%,,,,114:,[5][6]2002,[7],2.810L406.90395.12LgöL(),(GGPP)20,,25A2210B2213A225A22O222A2Ë210B2O23223232N22222[8]115:,,,,1993Taxusmediacv1Hicksii,,,,,,T1cuspidataSieb1etZncc1()T1baccataL1()0.017%[9]0.046%[10],(0.015%)35,,199623000,,,95%[1113][14][15],10001500m,,30;-13,,,,,,2(camptothecin,CPT)WallWani1996CamptothecaacuminataDecne.211:É(topoi2someraseÉ)[16,17],STopoÉ,DNA,DNA,,212:,(2)2Fig.2Structureofcamptothecin21211ABC:1)C2791011,710,(humanserumalbumin,HAS),[18]2)C27682ChineseTraditionalandHerbalDrugs382200729;C2910;C21011,[19]3)C2512144)B,21212DE:1)20,,2)D;3)20(S)20(R)10100[4]4)E,E,;5)EA,6)EAD,[20]213:,,,,,,,[21],14,,[22],NMR,CPT,,(strictosidinesynthaseSSS),,CPT,,BC,,3,,3(vinblastine)Catha2ranthusroseus(L1)G1Don311:,,,,,[23]312(3)31211(vindoline)3Fig.3StructureofvinblastineF:N2CH3()N2CHO[(vincristine)]N21,G:1)C23R1422C23,(vindesine)R1N,N,N22)C24N,N2,[24]I:C26C27,31212(caranthadine)C:1)722),DC23C24,(vinorelbine),,[25]3)18D:C24,DR2202,(vin2flunine),P2,,[26]CG,CC24GC23C24;C22RC24SC218S[27]313:(tryptoophandecarboxylase,TDC),102(geraniol210hydroxylase,G10H)102,[28],[29],,G10H,SSS,TDC(tabersonine),(O2methyltransferase,OMT)1622O2(162hydroxytabersonine2O2methyltransferase,16HT2OMT)[30],Hong[31](terpenoidindolealkaloids,TIAs)782ChineseTraditionalandHerbalDrugs38220072,,,,,TDC,[32]Whitmer[33],TDCT22TIAsXu[34](sodiumnitroprusside,Na2[Fe(CN)5NO])NO,TIAs,,,4(resveratrol,Res),[35][36],(podophyllotoxin),:(1)C24,,,M;(2)C24,DNAÊ,G[37][38],C24C24[39],Sinopodophyllumemodi(Wall1)Ying,,,,5,,40%[40],,;,,,,,,,,References:[1]RowinskyEK1Thedevelopmentandclinicalutilityofthetaxaneclassofantimicrotublechemotherapyagents[J]1An2nuRevMed,1997,48:35323741[2]RaoS,KraussNE,HeerdingJM,etal132(p2Azidobenzo2mido)taxolphotolabelstheN2teminal31aminoacidsofp2tubulin[J]1JBiolChem,1994,269(5):312321[3]DamenEWP,WiegerinckPHG,BraamerL,etal1Pacli2taxelestersofmalicacidasprodrugswithimprovedwatersolubility[J]1BioorgMedChem,2000,8(2):4271[4]SrivastavaV,NegiAS,KumarJK,etal1Plant2basedanti2cancermolecules:Achemicalandbiologicalprofileofsomeimportantleads[J]1BioorgMedChem,2005,13:5892259081[5]HuK,HeY,ZhuSQ,etal1Progressoftaxolbiosynthesisincellsuspensioncultureoftaxus[J]1NatProResDev(),2003,15(5):47124751[6]HuK,TanF,TangKX,etal1IsolationandscreeningofendophyticfungibreedinguptaxolfromTaxusmairei[J]1JSouthwestChinaNormUniv:NatSci(:),2006,31(1):13421371[7]LiuXL,ZhouDP,SunJQ,etal1Astudyonfermentationprocessforproductionoftaxolbynodulisporiumsylviforme[J]1Mycosystema(),2002,21(2):24622511[8]SunQP,ZhaoFK,GuanXL,etal1AreviewonenzymesrelatedtoTaxolbiosynthesis[J]1JBeijingAgrcColl(),2005,20(3):672721[9]CraggGM,SaulAS,MattewS,etal1Thetaxolsupplycrisis:NewNCIpolicesforhandingthelarge2scaleproduc2tionofnovelnaturalproductanticancerandanti2HIV[J]1JNatProd,1993,56(10):1657216681[10]CastorTP,TheodoreAT1DeterminationoftaxolinTaxusmedianeedlesinthepressenceofinterferingcomponents[J]1JLiqChromatogr,1993,16(3):72327311[11]TanF,PangYZ,XiongNX,etal1Introduction,propaga2tionandtaxolsaccumulationinleavesofTaxusmedia[J]1JSouthwestChinaNormUniv:NatSci(:),2000,25(4):44824511[12]LuZG,ZhouWJ,ZhaoCQ,etal1Studiesontheadapta2tionofTaxusmediacv1Hicksiitonaturaltemperaturereduc2tion[J]1ActaPhytoecolSin(),2004,28(1):732771[13]ZhaoCQ,LuZG,HanY,etal1PhysiologicaladaptationofmembraneprotectivesystemtosoilwaterstressinTaxusme2diacv1Hicksii[J]1JSouthwestChinaNorUniv:NatSci(:),2003,28(1):11221161[14]GabettaB,PeterlongoF,ZiniG,etal1TaxanesfromTaxusmedia[J]1Phytochemistry,1995,40(6):1825218281[15]ZhuSQ,TanF,TangKX1Technologyprogressonextrac2tionandpurificationoftaxol[J]1ChinJBiochemPharm(),2004,25(1):592621[16]PommierY1DiversityofDNAtopoisomerasesIandin2hibitors[J]1Biochimie,1998,80:25522701[17]PommierY,RedonC,RaoVA,etal1Repairofandcheck2pointresponsetotopoisomeraseI2mediatedDNAdamage[J]1MutatRes,2003(532):17322031[18]PanXD,WangCY1Currentstatusofcamptothecinderiva2tivesasnaturalantitumoragents[J]1ActaPharmSin(),2003,38(9):71527201[19]GaoHY,ZhangXW,ChenY1Synthesisandantitumorac2tivit