Identification and evaluation of apoptotic compounds from Garcinia oligantha

Four new compounds, oliganthins A-D (1-4), and one known caged xanthone gaudichaudione H (5) were isolated from the stems of Garcinia oligantha. The structures of the new compounds were elucidated by spectroscopic evidences. All of the five compounds were evaluated for their apoptosis-inducing effects using HeLa-C3 cells which have been genetically engineered to produce a fluorescent biosensor capable of detecting caspase-3 activation. All of them induced cell apoptosis at 10 μM or lower concentrations. The apoptotic activity of oliganthins A, B and gaudichaudione H were further confirmed by detecting the cleavage of PARP, which is the substrate of activated caspase-3, in these compounds-treated cells using the method of Western blot. Moreover, the values of IC(50) were measured for all five compounds on HeLa cells using the MTT assay. Among them, gaudichaudione H had the lowest IC(50) value of 0.90 μM, while the other four new compounds had IC(50) values of 1.58, 1.52, 4.15, and 7.82 μM, respectively. These results show that gaudichaudione H has the strongest apoptosis-inducing effect and cell growth inhibition effect among these xanthones and it may have the potential to be developed into a new anticancer agent.     

Phenolic compounds from the flowers of Garcinia dulcis

Dulcisxanthones C-F and dulcinone together with 22 known compounds were isolated from the flowers of Garcinia dulcis. Their structures were determined by spectroscopic methods. The abilities of some of these compounds to act as radical scavengers and antibacterial agents were investigated.     

Phenolic compounds from the fruit of Garcinia dulcis

Dulcinoside (1), dulcisisoflavone (2), dulcisxanthone A (3) and sphaerobioside acetate (6) together with 22 known compounds were isolated from the green fruit of G. dulcis. Dulcisflavan (4), dulcisxanthone B (5) and isonormangostin (7) together with 22 known compounds were isolated from the ripe fruit. Compounds 6 and 7 were synthetic known compounds. Their structures were determined by spectroscopic methods. The radical scavenging and antibacterial activities of some of the compounds were investigated.     

Cytotoxic prenylated phenolic compounds from the twig bark of Garcinia xanthochymus

Three new hydroxylated xanthones with prenyl or geranyl substituents, compounds 1-3, were isolated from the twig bark of Garcinia xanthochymus, along with the four known compounds 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone (4), 1,3,5,6-tetrahydroxy-4,7,8-triprenylxanthone (5), garciniaxanthone E (6), and 6-prenylapigenin (7). Their structures were elucidated by extensive spectroscopic analysis, including 1D- and 2D-NMR as well as HR-MS experiments. All compounds showed moderate cytotoxicities against breast cancer (MDA-MB-435S) and lung adenocarcinoma (A549) cell lines, but lacked antifungal activity against Candida albicans.     

Inhibition of acidic sphingomyelinase by xanthone compounds isolated from Garcinia speciosa

Sphingomyelinase is considered to be involved in the regulation of apoptosis and cell growth. In the course of our screening for acidic sphingomyelinase inhibitors we isolated three xanthone compounds, alpha-mangostin, cowanin, and cowanol, from the bark of Garcinia speciosa. These compounds competitively inhibited bovine brain-derived acidic sphingomyelinase with IC(50) values of 14.1, 19.2, and 10.9 microM, respectively and inhibited the acidic sphingomyelinase more effectively than the neutral sphingomyelinase of bovine brain. alpha-Mangostin inhibited the acidic sphingomyelinase in the most selective manner. alpha-Mangostin was chemically modified and its structure-activity relationships are discussed.     

Xanthones and benzophenones from Garcinia griffithii and Garcinia mangostana

A new polyisoprenylated benzophenone, guttiferone I, together with the known compounds cambogin, 1,7-dihydroxyxanthone, 1,3,6,7-tetrahydroxyxanthone and 1,3,5,6-tetrahydroxyxanthone were isolated from the stem bark of Garcinia griffithii. The acetone extract of the heartwood of Garcinia mangostana contained one new diprenylated xanthone (mangoxanthone) and a new benzophenone (3',6-dihydroxy-2,4,4'-trimethoxybenzophenone) as well as the known xanthones dulxanthone D, 1,3,7-trihydroxy-2-methoxyxanthone, 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran[7,6-b]xanthen-9-one. Their structures were established on the basis of spectroscopic studies and chemical correlation.     

Identification of odorous compounds from Streptomyces avermitilis

Summary The production of avermectin-type antibiotics and the odours of a strain ofStreptomyces avermitilis was investigated. With the increasing production of the total of avermectins (0–600 ug/ml), the synthesis of geosmin is also enhanced by more than one order of magnitude and, in contrast, the production of homologues of oxolone (dihydrofuranone) decreases in a similar range. In addition to these compounds, more than twenty other volatile chemical products have been identified by means GC-MS,i.e. pyrazine derivatives, acetoin and its homologues, aromatic esters, furan derivatives,etc.).     

Xanthones from three Garcinia species

From the stem bark of three previously uninvestigated Garcinia species a number of xanthones have been isolated including three that appear to be novel. The novel compounds are characterized as isocowanin (8-geranyl-4-(3,3-dimethylallyl)-7-methoxy-1,3,6-trihydroxyxanthone), isocowanol (8-geranyl-4-(3-hydroxymethyl-3-methylallyl)-7-methoxy-1,3,6-trihydroxyxanthone) and nervosaxanthone (4,8-di(3,3-dimethylallyl)-2-(1,1-dimethylallyl)-1,3,5,6-tetrahydroxyxanthone). The chemotaxonomic significance of oxygenation patterns in these xanthones is briefly discussed.     

Prenylated xanthones and tocotrienols from Garcinia virgata

Two xanthones, namely virgataxanthone A and B, have been isolated from the stem bark of Garcinia virgata, together with two formylated tocotrienols and the known delta-tocotrienol, griffipavixanthone and 2,6-dihydroxy-4-methoxybenzophenone (cotoin). Their structures were mainly established using one and two-dimensional NMR and mass spectroscopies. When sufficient material was available, the antioxidant activities of the crude extracts as well as the isolated compounds were evaluated.     

Cytotoxic benzophenone and triterpene from Garcinia hombroniana

Garcinia hombroniana (seashore mangosteen) in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to investigate the bioactive chemical constituents of the bark of G. hombroniana. Ethyl acetate and dichloromethane extracts of G. hombroniana yielded two new (1, 9) and thirteen known compounds which were characterized by the spectral techniques of NMR, UV, IR and EI/ESI-MS, and identified as; 2,3′,4,5′-tetrahydroxy-6-methoxybenzophenone (1), 2,3′,4,4′-tetrahydroxy-6-methoxybenzophenone (2), 2,3′,4,6-tetrahydroxybenzophenone (3), 1,3,6,7-tetrahydroxyxanthone (4), 3,3′,4′,5,7-pentahydroxyflavone (5), 3,3′,5,5′,7-pentahydroxyflavanone (6), 3,3′,4′,5,5′,7-hexahydroxyflavone (7), 4′,5,7-trihydroxyflavanone-7-rutinoside (8), 18(13 → 17)-abeo-3β-acetoxy-9α,13β-lanost-24E-en-26-oic acid (9), garcihombronane B (10), garcihombronane D (11), friedelan-3-one (12), lupeol (13), stigmasterol (14) and stigmasterol glucoside (15). In the in vitro cytotoxicity against MCF-7, DBTRG, U2OS and PC-3 cell lines, compounds 1 and 9 displayed good cytotoxic effects against DBTRG cancer cell lines. Compounds 1–8 were also found to possess significant antioxidant activities. Owing to these properties, this study can be further extended to explore more significant bioactive components of this plant.     

Cytotoxic xanthones from Garcinia penangiana Pierre

Two new xanthones, characterized as 4-(1,1-dimethylprop-2-enyl)-1,3,5,8-tetrahydroxyxanthone (1) and penangianaxanthone (2), with three known xanthones, cudratricusxanthone H (3), macluraxanthone C (4) and gerontoxanthone C (5), as well as friedelin and stigmasterol were isolated from the leaves of Garcinia penangiana. Their structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with the literature ones. Significant cytotoxicity against DU-145, MCF-7 and NCI-H460 cancer cell lines was demonstrated by compounds 1-5, with IC50 values ranging from 3.5 to 72.8 microM.     

Sorbifolin 6-galactoside from Garcinia andamanica

A new flavone glycoside, sorbifolin 6-galactoside, has been isolated from the leaves of Garcinia andamanica along with the known scutellarein 7-diglucoside. Their structures were established using spectroscopic and chemical evidence.     

Xanthones from the bark of Garcinia pedunculata

Three new xanthones, pedunxanthones A–C (1–3), together with five known compounds, 1,5-dihydroxy-3-methoxy-6′,6′-dimethyl-2H-pyrano(2′,3′:6,7)-4-(3-methylbut-2-enyl)xanthone, 1,5-dihydroxy-3-methoxy-4-(3-methylbut-2-enyl)xanthone, dulxanthone A, garbogiol and oleanolic acid, were obtained from a petroleum ether extract of the bark of Garcinia pedunculata. The new structures were elucidated using spectroscopic methods, mainly 1-D and 2-D NMR.     

Antimalarial xanthones from Calophyllum caledonicum and Garcinia vieillardii

The antimalarial activity of 22 xanthones against chloroquino-resistant strains of Plasmodium falciparum was evaluated. Natural caloxanthone C (1), demethylcalabaxanthone (2), calothwaitesixanthone (3), calozeyloxanthone (4), dombakinaxanthone (5), macluraxanthone (6), and 6-deoxy-gamma-mangostin (7) were isolated from Calophyllum caledonicum. 1,6-dihydroxyxanthone (8), pancixanthone A (9), isocudraniaxanthone B (10), isocudraniaxanthone A (11), 2-deprenylrheediaxanthone B (12) and 1,4,5-trihydroxyxanthone (13) were isolated from Garcinia vieillardii. Moreover, synthetic compounds (14-22) are analogues or intermediates of xanthones purified from Calophyllum caledonicum (Oger J.M., Morel C., Helesbeux J.J., Litaudon M., Seraphin D., Dartiguelongue C., Larcher G., Richomme P., Duval O. 2003. First 2-Hydroxy-3-Methylbut-3-Enyl substituted xanthones isolated from Plants: structure elucidation, synthesis and antifungal activity. Natural Product Research 17(3), 195-199; Helesbeux J.J., Duval O., Dartiguelongue C., Seraphin D., Oger J.M., Richomme P., 2004. Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors. Tetrahedron 60(10), 2293-2300). The relationship between antimalarial activity and molecular structure of xanthones has also been explored. The most potent xanthones (2), (3) and (7) (IC50 = c.a. 1.0 microg/mL) are 1,3,7 trioxygenated and prenylated on the positions 2 and 8.     

Xanthones and triterpenoids from the bark of Garcinia vilersiana

The hexane extract of the bark of Garcinia vilersiana from Vietnam contained four triterpenoids (olean-12-ene-3beta,11alpha-diol, lupeol, beta-amyrin and oleanolic acid), and six xanthones (globuxanthone, subelliptenone H, subelliptenone B, 12b-hydroxy-des-D-garcigerrin A, 1-O-methylglobuxanthone and symphoxanthone). The structure of 1-O-methylglobuxanthone, the only novel compound, was determined using 1D and 2D NMR techniques and by correlation with globuxanthone.     

Lanostanes and friedolanostanes from the bark of Garcinia speciosa

The CHCl(3) extract of the bark of Garcinia speciosa contained four 17,14-friedolanostanes and five lanostanes as well as friedelin and common plant constituents. The friedolanostanes were the previously known methyl ester of (24E)-3 alpha,23 alpha-dihydroxy-17,14-friedolanostan-8,14,24-trien-26-oic acid and the methyl esters of three hitherto unknown acids, 3 alpha-hydroxy-16 alpha,23 alpha-epoxy-17,14-friedolanostan-8,14,24-trien-26-oic acid, 3 alpha,23 alpha-dihydroxy-8 alpha,9 alpha-epoxy-17,14-friedolanostan-15-oxo-24-en-26-oic acid and 3 alpha,23 alpha-dihydroxy-17,14-friedolanostan-15-oxo-8(14),24-dien-26-oic acid. New lanostanes were 3 beta,9 alpha-dihydroxylanost-24-en-26-al and the methyl ester of 3 beta-hydroxy-23-oxo-9,16-lanostadien-26-oic acid. Structures were established by analysis of spectroscopic data. In the case of the lanostanes the previously unassigned C-25 stereochemistry was shown to be 25R by X-ray analysis of 3 beta-hydroxy-23-oxo-9,16-lanostadien-26-oic acid. In the case of the friedolanostanes the configuration at C-23 was established as 23R, identical with the absolute configuration at C-23 of mariesiic acids A and B.