Chemical Constituents Of Garcinia Hanburyi And G. Tetralata And Their Antitumor Activities

Garcinia hanburyi Hook.f.,a plant belonging to the family of Guttiferae,is distributed throughout Thailand,Cambodia,and the southern part of China.Its resin is used as a dye and as a folk medicine for purgative and for the treatment of infected wounds,and has been developed as an anti-tumor drug in China.G.tetralata is distributed in the Yunnan province of China.No previous phytochemical investigations were focused on G.tetralata.Based on the review on the chemical constituents and pharmacological research of Garcinia,the chemical constituents of Garcinia hanburyi and G.tetralata and their antitumor activities were researched.By means of many different chromatographic methods such as silica gel, Sephadex LH-20,ODS column chromatography,and preparative TLC,17 compounds were isolated from the resin of Garcinia hanburyi.By physico-chemical data and spectral methods,these compounds were identified as 2α-hydroxy-3β-O-acetyl-lup-20(29)-en-28-oic acid(1),3-O-(4'-O-acetyl)-α-L-arabinopyranosyl-oleanolic acid(2),gambogic aldehyde(3),forbesione(4),hanburin (5),desoxygambogenin(6),isogambogenin(7),desoxymorellin(8),isomorellin(9),β-morellic acid(10),α-morellic acid(11),gambogellic acid(12),gambogic acid(13), 30-hydroxygambogic acid(14),betulinic acid(15),messagenic acid(16),andβ-sitosterol(17).Among them,compounds 1～3 are determined as new compounds, compound 16 is obtained from genus Garcinia for the first time.By means of many different chromatographic methods,22 compounds were isolated from the barks of Garcinia tetralata.Twenty of them were characterized by physico-chemical data and spectral methods,and they were 3β-hydroxy-18β, 19β-epoxy-lupane(18),tetralataxanthone(19),2-(1',1'-dimethylprop-2'-enyl)-1,4, 5-trihydroxy-9H-xanthen-9-one(20),6-desoxyjacareubin(21),toxyloxanthone A(22), globuxanthone(23),1,7-dihydroxyxanthone(24),subelliptenone H(25), 6-deoxyjacreubin(26),buchanaxanthone(27),garciniaxanthone H(28),6, 11-dihydroxy-2,2-dimethyl-pyrano[3,2-c]xanthen-7(2H)-one(29),subelliptenone G (30),1,4-dihydroxy-5,6-dimethoxyxanthone(31),1,2,5-trihydroxyxanthone(32),2, 6-dihydroxy-1,5-dimethoxyxanthone(33),morolic acid acetate(34),methyl orsellinate(35),montroumarin(36),andβ-sitosterol(37).Among them,compounds 18 and 19 are determined as new compounds,compounds 34～36 are isolated from genus Garcinia for the first time. The antitumor activities of the two new triterpenoids and twelve caged polyprenylated xanthones isolated from the resin of Garcinia hanburyi were tested.It was found that all caged polyprenylated xanthones inhibited cell growth with different activities against P388 and P388/ADR cells,in which compounds 12 and 13 were the most potent.The structure-activity relationship of caged polyprenylated xanthones was discussed.The results showed that the presence of pyran-ring in the molecular might have an important role in inhibiting P388 cell line.If the pyran-ring had 2-isoprenyl group,the activity would be enhanced.To the xanthones which had not a pyran-ring(6～7),those with the substituent of 5-geranyl group could have better activity in inhibiting P388 cell line.By testing in human leukemia HL-60,NB4,U937, K562 cells,it was found that two new triterpenes were effective cell growth inhibitors. Compound 2 showed more potent activity than compound 1.The apoptotic effects in HL-60 cells were also examined by morphological observation after AO and EB staining and FACS analysis.The two new triterpenoids induced HL-60 cells to undergo apoptosis in a dose- and time-dependent manner.On the basis of the research on caged polyprenylated xanthones isolated from the resin of Garcinia hanburyi and the related literatures,an overview on the spectral and structural characteristics of caged polyprenylated xanthones was taken.