β-咔啉類生物堿抗腫瘤活性及其機(jī)理的初步研究.pdf

1、中山大學(xué)碩士學(xué)位論文β咔啉類生物堿抗腫瘤活性及其機(jī)理的初步研究姓名：侯雪瑞申請學(xué)位級(jí)別：碩士專業(yè)：生物化學(xué)與分子生物學(xué)指導(dǎo)教師：徐安龍20040602PreliminaryResearchinAntitumorActivitiesandtherelatedMolecularMechanismsofBetacarbolinealkaloidsAbstractCancerhasbecomeoneofthemostserviousdiseas

2、esthatthreateningpeople’SlifeintheworldOneoftheimportantmethodsforthediscoveryofDewdrugsofantitumoristoidentifynaturalproductswhichhaveantitttmoractivitythenmodifythestructureofthemforbetteractivityandlesstoxicityBetacar

3、bolinesareselectedforthisstudysincetheyarereportedtohaveantitumoractivitiesonculturedcanceicelllinesFirst，acomparativemolecularfieldanalysis(CoMFA)studywasundertakentoelucidatethecorrelationofcytotoxitiesandstructuralpar

4、ametersofi6beta—carbolineanalogsSomecompoundsthathadbeenstruturallymodifiedwerefoundtOhavesignificantantitumoractivitiesthroughafastscreeningsysteminvitroforantitumorcompoundsBaseontheresultsofit，testsonanimalmodelswereu

5、ndertakeninvivo，anon—toxicandthehighesteffectivecompound36wasobtainedwitllinhibitioneffectagainstLewislungcancerat469％Alsotwohigheffectiveandlowtoxiconescompounds11and33wereobtainedwithinhibitioneffectagainstbothsarcomaS

6、180andLewislungcancerover40％SecondlyastudyofthesecompoundsonthereverseofHCT15(HCT8／Tax01)cellline’SmultidrugresistancewasundertakenCompound65changedlittletoxicityoftaxoltoHCT8，butitimprovedthesensitivityofHCT15(HCT8／Tax0