Xanthones from the bark of Garcinia Xanthochymus

Two novel xanthones, 1,6-dihydroxy-4,5-dimethoxyxanthone （1） and 1,5,6-trihydroxy-7,8-di（3-methyl-2-butenyl）-6＇,6＇-dimethylpyrano（2＇,3＇：3,4）xanthone （2） were isolated from the bark of Garcinia xanthochymus by normal phase and reverse phase silica gel column chromatography. Their structures were elucidated by spectroscopic methods, especially 2D-NMR techniques.

Apoptotic activity of caged xanthones from Garcinia hanburyi in cholangiocarcinoma cell lines

AIM:To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma(CCA) KKU-100 and KKU-M156 cells.METHODS:Four caged xanthones,selected on the basis of their anticancer potency and chemical structure diversities(i.e.isomorellin,isomorellinol,forbesione and gambogic acid) were used in this study.Growth inhibition of these caged xanthones was determined using the sulforhodamine B assay.Induction of apoptosis was assessed by observing cell morphology,ethidium bromide and acridine orange staining and DNA fragmentation assay.Levels of apoptotic-related gene and protein expressions were determined by a real-time reverse transcriptase polymerase chain reaction and Western blotting analysis,respectively.RESULTS:The compounds were found to inhibit growth of both cell lines in a dose-dependent manner and also showed selective cytotoxicity against the cancer cells when compared with normal peripheral blood mononuclear cells.Growth suppression by these compounds was due to apoptosis,as evidenced by the cell morphological changes,chromatin condensation,nuclear fragmentation,and DNA ladder formation.At the molecular level,these compounds induced down-regulation of Bcl-2 and survivin proteins with up-regulation of Bax and apoptosisinducing factor proteins,leading to the activation of caspase-9 and-3 and DNA fragmentation.The functional group variations did not appear to affect the anticancer activity with regard to the two CCA cell lines;however,at a mechanistic level,isomorellinol exhibited the highest potency in increasing the Bax/Bcl-2 protein expression ratio(120 and 41.4 for KKU-100 and KKU-M156,respectively) and in decreasing survivin protein expression(0.01 fold as compared to control cells in both cell lines).Other activities at the molecular level indicate that functional groups on the prenyl side chain may be important.CONCLUSION:Our findings for the first time demonstrate that four caged xanthones induce apoptosis in CCA cells which is mediated through a mitochondriadependent signaling pathway.

Optimized Separation of Pharmacologically Active Xanthones from Securidaca inappendiculata by Capillary Electrophoresis

A capillary electrophoresis (CE) method has been firstly used for the separation of the therapeutically important xanthones from Securidaca inappendiculata. The separation of the nine xanthones was systematically optimized with respect to pH, concentration of running buffers, addition of sulfated b-CD, applied voltage and column temperature. Baseline separation was achieved for the nine xanthones in less than 15 minutes using a background electrolyte consisting of 200 mmol/L borate (pH 9.5) and 10 mmol/L sulfated b-CD.

Optimized Separation of Nine Xanthones by Microemulsion Electrokinetic Chromatography

A microemulsion electrokinetic chromatography method has been firstly used for the separation of the therapeutically important xanthones from Securidaca inappendiculata. The separation of the nine xanthones was systematically optimized with respect to pH, composition of microemulsion, addition of cyclodextrins, applied voltage and column temperature. Baseline separation was successfully achieved for the nine xanthones, which was also compared with that by micellar electrokinetic chromatography.

New Xanthones from Polygala crotalarioides

Introduction Xanthones are secondary metabolites commonly occurring in a few higher plant families, fungi and lichen. Their high taxonomic value in such families and their pharmacological properties, including in vitro cytotoxicity, in vivo antitumour activity, antifungal, antibacterial, antiinflammatory properties and aldose reductase inhibitory activity have provoked great interest. The discovery of the antidiabetic activity of some axnthones＇ from Swertiaceae has prompted us to undertake a more broadly search for novel xanthones from plants of Polygalaceae. The phytochemical investigation has not been performed on this plant up to now. Herein we report the isolation and structure elucidation of two new xanthones （ compounds 1 and 2 ） and three known xanthones （compound 3, 4 and 5 ）.

Study on the Intramolecular Hydrogen Bonds of Dibenzofurans, Xanthones and Anthraquinones with One or Two Positions Substituted by Hydroxyls

The thermodynamic properties of dibenzofurans （DFs）, xanthones （XTs） and an-thraquinones （AQs） with one and two positions substituted with hydroxyls in the ideal gas state at 298.15 K and 1.013×10^5 pa were calculated at the B3LYP/6-311G^＊ level using Gaussian 03 program. The isodesmic reactions were designed to calculate the standard free energy of formation （△fG^θ）. Three types of hydrogen bonds exist in the three kinds of chemicals and their bond energies were ascertained as 7-15, 15-23 and 49-58 kJ·mo1^-1 respectively by comparing the △fG^θ values. Electronic density topology analysis was applied to validate the strength of bond.

Activity of xanthones isolated from Lomatogonium rotatum

Thirteen xanthones were isolated from L.rotatum,which were established as l,8-dihydroxy-3,4,5-trimethoxyxanthone(1);l-hydroxy-3异,8-trimethoxyxanthone(2);8-hydroxy-l,3?5-trimethoxyxaiithone(3);l-hydroxy-3,4,5-trimethoxyxanthone(4);l-hydroxy-3,5,8-trimethoxyxanthone(5);l,4,8-trihydroxy-5,6-dimethoxyxanthone(6);l,3,8-trihydroxy-4,7-dimethoxyxanthone(;7)l,8-dihydroxy-3,7-dimethoxyxanthone(8);l-hydroxy-3,5-dimethoxyxanthone(9);l-hydroxy-2,3,4,5-tetramethoxyxanthone(;10)l-hydroxy-2,3,4,7-tetramethoxyxanthone(11);l,7-dihydroxy-3,8-dimethoxyxanthone(12);rel-l,3,5,8-tetrahydroxy-2,4,6,7-tetrahydroxanthen-9-one(13).Compounds 4,6,7,9,10,11,12 and 13 are reported for the first time from Lomatogonium.Furthermore,the activity of xanthones was assessed.

Isolation and Crystal Structure of Xanthones from Swertia Chirayita

In order to study the relationship between biological and pharmacological activities with their structures, a series of tri- and tetra-oxygenated xanthones including 1-hydroxyl-2,3,4,7- tetramethoxy xanthone 1, 1-hydroxyl-2,3,4,5-tetramethoxyl xanthone 2, 1-hydroxyl-3,5-dimethoxy- xanthone 3, 1,8-dihydroxyl-3,5-dimethoxyl xanthone 4 and 1,5,8-trihydroxyl-3-methoxy xanthone 5 have been isolated from Swertia chirayita. Their structures were established on the basis of spectral and chemical evidences. The crystal structure of 5 was also investigated by single-crystal X-ray diffraction analysis. It crystallizes in the triclinic system, space group P?with a = 7.1540(10), b = 7.520(2), c = 10.671(2) , V = 562.7(2) 3 , α = 86.50(3), β = 80.06(3) , γ = 85.00(3), Z = 2, Dc = 1.618 g/m3, R = 0.0405, wR = 0.1028 and F(000) = 284. The molecular structure of 5 is nearly planar and four substituents are much closer to the plane. Compound 5 contains three intermolecular hydro- gen bonds. A recent study shows that phenolic hydroxyls in xanthones are the main active groups capable of scavenging OH and O2.

Studies of Thermodynamic Properties and Relative Stability of Polybrominated Xanthones by Density Functional Theory

The thermodynamic properties of xanthone（XTH） and 135 polybrominated xanthones（PBXTHs） in the standard state have been calculated at the B3LYP/6-31G＊ level using Gaussian 03 program.The isodesmic reactions were designed to calculate the standard enthalpy of formation（△fHθ） and standard free energy of formation（△fGθ） of PBXTH congeners.The relations of these thermodynamic parameters with the number and position of Br atom substitution（NPBS） were discussed,and it was found that there exist high correlation between thermodynamic parameters（entropy（Sθ）,△fHθ and △fGθ） and NPBS.According to the relative magnitude of their △fGθ,the relative stability order of PBXTH congeners was theoretically proposed.The relative rate constants of formation reactions of PBXTH congeners were calculated,Moreover,the values of molar heat capacity at constant pressure（Cp,m） from 200 to 1000 K for PBXTH congeners were also calculated,and the temperature dependence relation of them was obtained,suggesting very good relationships between Cp,m and temperature（T,T^1 and T^2） for almost all PBXTH congeners.

Quantification of Flavonoids,Naphthopyranones and Xanthones in Eriocaulaceae Species by LC-PDA

The linearity, stability, accuracy and inter-day precisions of the assay method were evaluated in methanolic aerial-part extracts of Paepalanthus giganteus and Syngontnhus nitens from the Eriocaulaceae family. Their small capitulae hinder morphological analysis, and thus complicate taxonomic studies of these species, which present anti-ulcer, antimutagenic and antioxidant activities. Taxonomic studies of these plants revealed that the Paepalanthus genus presents flavonols and naphthopyranones while the Syngontnhus genus has flavone and xanthone as majority compounds. The prepared samples were analyzed quantitatively by High Performance Liquid Chromatography with PDA detection for the presence of quercetin, luteolin, 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and paepalantine. The substances were recovered from these samples at rates from 98.01 to 99.99%. The coefficient of variation in the quantitative analysis of the sample com- pounds was under 5%. The linearity of the method was determined by linear regression. The analysis of the samples spiked with known amounts of analyte demonstrated that the response was proportional to the concentrations of the sam- ples with re-spective determination coefficients of r2 = 0.9999 (luteolin and 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone) and r2 = 0.9998 (quercetin and paepalantine) for the linear range of the analytical calibration curves of the samples. The detection limits were 0.07 μg?mL–1 for quercetin and luteolin, 0.06 μg?mL–1 for 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and 0.10 μg?mL–1 for paepalantine. The quantification limits were 0.23 μg?mL–1 for quercetin and luteolin, 0.20 μg?mL–1 for 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and 0.33 μg?mL–1 for paepalantine by LC. The method was considered sen- sitive for quantification of the quercetin, luteolin, 3,6-dimethoxy-1,5,7-tri-hydroxyxanthone and paepalantine in plant samples.

Two new xanthones from Lomatogonium carinthiacum

AIM: To study the chemical constituents of Lomatogonium carinthiacum(Wulfen) Rchb. METHOD: The CHCl3-soluble fraction was separated by chromatography and the structures of the new compounds were elucidated by spectral experiments. RESULTS: Two new xanthones, 1, 8-dihydroxy-4, 5-dimethoxy-6, 7-methylenedioxyxanthone(1), 1, 4, 8-trimethoxyxanthone-6-O-β-D-glucoronyl-(1→6)O-β-D-glucoside(2) were isolated from the whole plant of Lomatogonium carinthiacum. CONCLUSION: Compounds 1 and 2 are new natural products.

Elodexanthones A—J, Isoprenylated Xanthone Derivatives with Diverse Skeletons and Bioactivities from Hypericum elodeoides

Elodexanthones A—J (1—10), two pairs of rearranged isoprenylated xanthone enantiomers with an unprecedent 6/6/5/6 tetracyclic core (1—2) along with seven new isoprenylated xanthones (3—9) and a pair of phenylpropanoid xanthones (10), were purified and enantio-separated from the whole plant of Hypericum elodeoides. Their structures including absolute configurations were characterized by the comprehensive analysis of NMR, HRESIMS, NMR calculations, and ECD calculations. Through Bayer-Villiger oxidation, Claisen condensation and electrophilic addition, the rearranged skeletons of elodexanthones A—B (1—2) were generated from isoprenylated xanthone precursors. The bioactivities evaluation exhibited that compounds 3, 5, 8—10 showed anti-inflammatory activity with the IC_(50) values in the range of 9.53—34.39 μmol/L, and compounds 3—7, and 9 showed notable α-glucosidase inhibitory activity (IC_(50): 6.02—257.11 μmol/L).

Cytotoxic 7-Methoxylated Caged Xanthones from the Twigs of Garcinia oligantha

Main observation and conclusion Nineteen unprecedented 7-methoxylated caged xanthones(1—19)were isolated from the twigs of Garcinia oligantha under the guidance of NMR spectroscopy.Their structures and absolute configurations were demonstrated by extensive spectroscopic data,single-crystal X-ray diffraction,electronic circular dichroism(ECD)calculations,and the modified Mosher's method.Compound 1 is a rare scalemic 7-methoxylated neo-caged xanthone,which was resolved using HPLC with CD detection on a chiral-phase AD column,and compounds 2—3 are rare 7-methoxylated caged xanthones with the hydrogenatedΔ^(8(8a))double bond.Fourteen compounds exhibited promising inhibitory activities against four human cancer cell lines with IC50 values ranging from 1.9 to 14.3μmol/L.A cell apoptosis analysis using flow cytometry showed that compound 11 could induce apoptosis in a dose dependent manner.Moreover,PARP,caspase-9,and Bcl-2 western blotting suggested that compound 11-induced apoptosis may be involved in caspase-dependent pathway.

Identification and characterization of two new xanthones from Cudrania fruticosa

The present study was designed to investigate the chemical constituents of the roots of Cudrania fruticosa Wight. Compounds were isolated by various column chromatographic methods including silica gel, polyamide, sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by a combination of 1D and 2D NMR techniques, mass spectrometry, and chemical methods. Two new xanthones, Cudraxanthone T and U(1-2), along with four known compounds(3-6) were isolated from the roots of Cudrania fruticosa Wight.

Bioactive xanthones from whole plants of Gentianella acuta

Objective： To study the constituents from the whole plants of Gentianella acuta and their biological activities.Methods： The compounds were isolated by multiple chromatographic methods and the structures of mentioned isolates were determined by routine NMR experiments and chemical methods.Results： A phytochemical investigation to obtain intestine motility inhibitor resulted in the isolation of one new xanthone glycoside,gentixanthonoside A（1）,along with nine tetrahydroxanthones,1,3,5R,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone（2）,1,3,5S,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone（3）,amarellin E（4）,amarellin F（5）,swertiachoside B（6）,amarellin D（7）,amarellin C（8）,amarellin A（9）,and amarellin B（10）from the whole plants of G.acuta.Conclusion： Compounds 2 –10 showed significant reduce effects on contraction tension at 40 μM.

Identification of the metabolites of biologically active xanthones isolated from Halenia elliptica D.Don by high performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry

Metabolism study has been carried out on 1-hydroxy-2,3,5-trimethoxyxanthone （HM-1） and 1-hydroxy-2,3,4,7- tetramethoxyxanthone （HM-2）, which are two biologically active ingredients isolated from the Tibetan herb, Halenia elliptica D. Don., in rat liver microsomes in vitro. A method of high performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry （LCMSn-ESI-IT-TOF） was applied to analyze metabolites of HM-1 and HM-2 on line, and five metabolites were identified containing 1,5-dihydroxy-2,3-dimethoxyxanthone （HM-5）, 1,7-dihydroxy-2,3,4-trimethoxyxanthone （HM-9）, 1,4, 7- trihydroxy-2,3-dimethoxyxanthone （HM-10）, 1,4-dihydroxy-2,3,7-trimethoxyxanthone （HM-11） and 1,2-dilaydroxy-3,4,7- trimethoxyxanthone （HM-12）. Among these metabolites, HM-9, HM-11, and HM-12 were isomers mutually. The results indicated that HM-1 and HM-2 occurred Phase I metabolic reaction of demethylation in rat microsomes in vitro.

Concise synthesis of xanthones by the tandem etherification——Acylation of diaryliodonium salts with salicylates

An efficient synthetic method for multi-substituted xanthones was developed. The reaction of diaryliodonium salts and salicylates was employed for the preparation of the xanthones. This method proceeded through an intermolecular etherification-acylation to give target heterocycles in good yields（up to 91%）. Multi-substituted xanthones were gained by shifting the substituent of salicylates or diaryliodonium salts

展萼金丝桃化学成分及其抗氧化活性研究

目的:对展萼金丝桃(Hypericum lancasteri N. Robson)的化学成分进行分离鉴定;对其单体化合物进行抗氧化活性评价。方法:展萼金丝桃干燥地上部分经粉碎,95%甲醇回流提取得总提取物,使用硅胶、凝胶、MCI、ODS柱色谱、高效液相色谱(HPLC)等多种分离技术对总提取物进行分离纯化,结合核磁共振氢谱(1H NMR)、碳谱(13C NMR)以及质谱(MS)等解析手段,通过文献数据分析确定所得化合物结构。采用DPPH自由基清除法对化合物1-4进行抗氧化活性评价。结果:共分离得到3个xanthone类化合物和2个其他类化合物,分别鉴定为1,7-dihydroxyxanthone (1), 2-hydroxyxanthone (2), 2,3-二甲氧基口山酮(3), hyperdioxanes B (4) 和2-methyl-6-isopropyl-7-hydroxymethyl naphthalene (5),化合物1-5均为首次从该植物中分离得到。化合物1-4在400 µmol/L浓度下的DPPH自由基清除率分别为11.44%,9.68%,11.04%,9.72%。结论:从展萼金丝桃地上部分分离得到5个单体化合物,均为首次从该植物中分离得到,丰富了该植物的物质基础,同时生物活性研究为展萼金丝桃在抗氧化活性方面的药物应用提供了线索。