Studies On Chemical Constituents Of Garcinia Paucinervis And Cratoxylum Cochinchinense And Their Biological Activities

Xanthones,benzophenones,acylphloroglucinols,depsidones,flavonoids(bi flavonoids),biphenyls,and triterpenoids are predominant sources of secondary metabolites in the Clusiaceae family.Some of these components exhibited diverse pharmacological properties.In recent years,the plants of this family have attracted the attention of scholars.In order to search for some biologically more-efficient constituents and fully develop the natural products of Chinese Clusiaceae resources,Garcinia paucinervis and Cratoxylum cochinchinense belonging to Clusiaceae were screened via the growth inhibitory activity against HL-60 cell line,TLC,NMR experiments and combined with the literature searching.The chemical constituents of two plants were investigated and biological activities were evaluated.By means of many different chromatographic methods such as macroporous resin,silica gel,polyamide,ODS,MCI,Sephadex LH-20 column chromatography,preparative TLC,semi-preparative HPLC,and chiral HPLC resolution,80 compounds were isolated from the 95%ethanol extract of the leaves of G.paucinervis,80%aqueous acetone extract of the stems of G.paucinervis and 80%aqueous acetone extract of the stems and leaves of C.cochinchinense.Their structures,including stereochemistry,were determined by spectroscopic analysis of IR,UV,MS,NMR,ECD calculation,the octantrule,and physico-chemical data.The compounds were comprised by 42 xanthones,5 benzophenones,3 depsidones,5 flavonoids and diflavonoids,9 triterpenes,9 phenolic acids,and 5 others.46 compounds were obtained from the leaves and stems of G.paucinervis,including 23 xanthones,5 benzophenones,2 depsidones,2 diflavonoids,4 triterpenoids,5 phenolic acids,and 5 others,thirteen of which are new compounds,named(±)paucinervins L-N(G1-G6),(-)paucinervin O(G7),paucinervin P(G8),paucinervin K(G24),paucinervin R(G25),(-)garpauvinin A(G26),paucinervin Q(G32),(-)23-hydroxy-friedelin(G33),respectively.The known compounds were identified as osajaxanthone(G9),garceduxanthone(G10),1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone(G11),bellidifodin(G12),parvifolixanthone A(G13),paucinervin I(G14),7-prenyljacareubin(G15),1,3,5-trihydroxy-4-prenylxanthone(G16),rheediaxanthone A(G17),pyranojacareubin(G18),1,3,5,6-tetrahydroxyxanthone(G19),2-isoprenyl-1,3,5,6-tetrahydroxyxanthone(G20),1,3,6,7-tetrahydroxyxanthone(G21),gentisin(G22),latisxanthone C(G23),30-epi-cambogin(G27),guttiferone K(G28),oblongifolin A(G29),thorelione A(G30),paucinervin B(G31),friedelin(G34),epifriedelanol(G35),friedelin-3,4-lactone(G36),benzoic acid(G37),p-coumaric acid(G38),p-hydroxybenzoic acid(G39),protocatechuic acid(G40),pyromeconic acid(G41),erigeside(G42),chlorogenic acid n-butyl ester(G43),dimethyl(2-methyl-1,3-phenylene)dicarbamate(G44),obtucarbamate A(G45),and 4,4’-diphenylmethane-bis(methyl)carbamate(G46).34 compounds were obtained from the stems and leaves of C.cochinchinense,including 23 xanthones,1 depsidone,1 flavonoid,3 triterpenoids,2 steroids,and 4 phenolic acids,two of which are new compounds,named(±)cracochxanthones A(C1,C2).The known compounds were identified as cochinchinone A(C3),1,6-dihydroxy-2,5,8-trimethoxyxanthone(C4),1,4,7-trihydroxy-8-methoxyxanthone(C5),gentisein(C6),xanthone V1(C7),1,3,7-trihydroxy-2,4-diisoprenylxanthone(C8),pruniflorone N(C9),dulcisxanthone B(C10),1,7-dihydroxyxanthone(C11),1,7-dihydroxy-8-methoxyxanthone(C12),1,5,6-trihydroxy-7-methoxyxanthone(C13),1,4,7-trihydroxyxanthone(C14),1,5,6-trihydroxy-3,7-dimethoxyxanthone(C15),cudratricusxanthone E(C16),cochinchinone B(C17),cochinchinone D(C18),γ-mangostin(C19),1,7-dihydroxy-4-methoxyxanthone(C20),1,3,6-trihydroxy-7-methoxyxanthone)(C21),1,7-dihydroxy-3,6-dimethoxyxanthone(C22),1,3,5-trihydroxy-6’,6’-dimethyl-2H-pyrano(2’,3:6,7)xanthone(C23),norstictic acid(C24),quercetin(C25),betulinic acid(C26),platanic acid(C27),3-O-acetyloleanolic acid(C28),stigmasterol(C29),5α-stigmast-3,6-dione(C30),aucuparin(C31),3,4-dihydroxybenzaldehyde(C32),3-methoxy-4-hydroxybenzoic acid(C33),and trans-caffeic acid(C34).Antiproliferative activities against HL-60,PC-3,HepG-2 and Caco-2 cell lines,antioxidant activities using DPPH and ABTS radicals scavenging capacities andα-glucosidase inhibitory activities in vitro were evaluated on some compounds isolated from G.paucinervis.The xanthone G8 with a fused furan ring was the most active against HL-60,PC-3 and Caco-2 cancer cells with IC50 values ranged from 0.87 to 12.23 μM.The xanthones G10 and G13 with two or three prenyl units showed high sensitivity against human malignant cell lines with IC50 values less than 5 μM.It is mentionable that the xanthone G3(with IC50 value of 1.45μM)with dextro-rotation exhibited more potent effect against HL-60 cell line than G4 with laevo-rotation(with IC50 value of 10.81 μM).The benzophenones G27 and G28 showed potent activities in all assays.Xanthones generally have antioxidant activities,such as compounds G9-11,G15,and G18 which displayed ABTS radical scavenging activities with IC50 values less than 10μM.The xanthone G10 exhibited potent α-glycosidase inhibition with IC50 value 8.90μM.Some of the compounds isolated from C.cochinchinense were measured for antitumor activities against HL-60,PC-3 and MDA-MB-231 cell lines.The xanthones C8,C10,C16 and C19 with two prenyls or xanthones C3,C17,C18 with one isoprenyl and one geranyl units showed favorable inhibitory effects on three cell lines with IC50 values ranging from 1.00-27.11 μM.