青蒿素類抗瘧藥物定量構(gòu)效關(guān)系研究.pdf

1、華南師范大學(xué)碩士學(xué)位論文青蒿素類抗瘧藥物定量構(gòu)效關(guān)系研究姓名：曾憲棟申請學(xué)位級別：碩士專業(yè)：物理化學(xué)指導(dǎo)教師：許旋20040601—————————————————。。?！猧!——j!!———————————————一——AbstractArtemisinin(Qinghaosu)wasfirstisolatedin1972fromArtemisiaannllaL；byChineseresearchersItisalleffec

2、tiveantimalarialagentagainstchloroquineresistantPlasmodiumfalcipanunstrainsandcerebralmalariaWithlowtoxicityInordertOdevelopmorepotent，betterwatersoluble，lessneurotoxicagents，alargemountofartemisininanalogshavebeensynthe

3、sizedbythesidechainchangingorstructuresimplifyingHoweverthedetailedmechanismofartemisininderivativesjselusiveInattemptstOunderstandthemechanismandtherelationshipoftheantimalarialactivitybetweentheirstructures，thequantita

4、tivestructureacfivityrelationshipswerestudiedinthisthesis91artemisimnderivatives’strdcturewerecalculatedbyHF／321GmethodandtheirquantumindiceswerecalculatedintheoryThemainconclusionsareasfollows：Theartemisinin’Sconformati

5、onscomparison，whichwereoptimizedbyseriesquantumchemistrymethodsrespectivelyandthecomparisonofchemicalshifts，whichwerepredictedbasedon10deoxoartemisinin’Sconformations，bothshowedthattheHF／3—21wasaquiteaccuratemethodConcer

6、ningtheaccuracyandthemountofCPUtime，HF／3—21GmethodwasselectedtooptimizetheartemisininanalogsforthebuildingofQSARmodel。Thequantumindiceswereextractedbasingonartemisininanalogues’electronicstructureThecomparativelysignific

7、antQSARmodelswerebuiltbyregressionanalysisThemodelsindicatedtllat：a。TheperoxobridgeisessentialbasegroupfortheantimalarialactivitybSupporttingthemechanismthatthecreationofthefreeradicalRO。onO(1)，cIncreasingthelengthofthes

8、ubstituentisconducivetoantimalarialaetivitybutthevolumeincreasingisdisadvantageousforthe10Oand16Csubstitutedartemisininanalogs，SOthefordedchainofsubstituentshouldbranchesattheheadgroupdTheRorSisomerisconducivetoantimalar