| This thesis consists of four chapters.In the first chapter,we have reviewed the chemical constituents in natural products with anti-multidrug resistance.The chemical constituents of aerial parts of Tripterygium hypoglaucum(Levl.)were investigated and discussed in the second chapter.Anti-tumor,reversal of multidrug resistance,and others bio-activities of the isolated compounds were evaluated in the third chapter.In the last chapter,we have made a summary on this thesis.Cancer is one of the most serious diseases that endanger human health.Although chemotherapeutic agents were effective in the early therapy of tumors,multidrug resistance of various cell would come out due to the long utilization of chemotherapeutic agents.Therefore,to overcome the multidrug resistance of tumor was the urgent problem in the process of tumor treatment,which has became the important topic in the discovery of the new drugs.Natural products have attracted great attention of researchers because they are rich in plant resource,low price,and low side effects.Our group had previously carried out the phytochemicals and bioactivities studies on the plants of T.hypoglaucum,the result found that diterpenes in the species showed significant anti-tumor and reversed multidrug resistance activities,which arouses us great interests.T.hypoglaucum is the plant of the genus Tripterygium(Celastraceae).According to the record in "Yunnan Chinese herbal medicine",T.hypoglaucum were mainly used for treatment of swelling,rheumatic arthritis,lupus erythematosus,and cancer.T.hypoglaucum contained abundant structure types,including dihydro-β-agarofuran sesquiterpenes,diterpenes,macrolide alkaloids,and flavonoid.By the means of various of chromatographic methods like silica gel,Sephadex LH20,ODS,MCI,RP-18 and MPLC,HPLC as well as spectroscopic technique(NMR,MS...),47 compounds were separated and identified from T.hypoglaucum,including 11 monoterpenes and sesquiterpenes,9 diterpenes,2 triterpenes,12 lignans,3 steroids,a flavonoid,a cyclohexanedione,and 8 other compounds,among which 7 compounds were new ones.Most isolated compounds were evaluated for anti-tumor,anti-flu virus and anti-inflammatory activities in vitro.Abietane-type diterpenoids with epoxypropane substructure,triptolide(23),showed potent cytotoxicity against HepG2(IC50=0.203 μM)and HepG2/ADR(IC50=2.662 μM).Four dihydro-β-agarofuran sesquiterpenes,triptogelin C-1(10)(RF=102.83 in 20 μM),triptogelin C-4(11)(RF=47.46 in 20 μM),1β-(a-methyl)-butanoyl-2β,6α,13-triacetoxy-9β-benzoyloxy-β-dihydroagarofuran(14)(RF=456.90 in 20 μM),and chiapen D(15)(RF=48.45 in 4μM)showed reversal activity of mutidrug resistance to HepG2/ADR with co-administration of adriamycin.Two abietane-type diterpenoids,triptobenzene J(19)and quinone 21(22)showed anti-flu viru activity against PR8(Oseltamivir resistant strain),with EC50 of 12.3±3.5 μg/ml and 7.5±2.1 μg/ml,respectively.It is interesting that 22 also showed moderate active against H3N2(VR1679)flu virus(EC50=7.1 ± 0.18 μg/ml).In addition,three abietane-type diterpenoids,triptophenolide(17)(IC50=4.90 μM),quinone 21(22)(IC50=2.58 μM),and triptolide(23)(IC50＝0.019μM)had potent anti-inflammatory activity.It was suggested that dihydro-β-agarofuran sesquiterpenes and abietane-type diterpenoids(with epoxypropane substructure)in T.hypoglaucum were responsible for reversal activity of tumor multidrug.Abietane-type diterpenoids(without epoxypropane substructure)had the anti-inflammatory and anti-flu virus activities. |
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