Bioactive cembrane diterpenoids of Anisomeles indica

Five new cembrane-type diterpenoids with a trans-fused alpha-methylene-gamma-lactone (1-5), a new flavonoid glucoside (6), and 17 known compounds were isolated from a methanol extract of Anisomeles indica. The structures of 1-6 were elucidated by spectroscopic analysis, and the absolute configuration of compound 1 was determined using the modified Mosher's method. Compound 8 (4,5-epoxovatodiolide) exhibited cytotoxicity against a small panel of human cancer cell lines. Additionally, compounds 4 and 7 (ovatodiolide) exhibited selective antiplatelet aggregation activities toward collagen, while compounds 4, 5, and 8 showed inhibitory effects on antiplatelet aggregation induced by thrombin.     

Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori

The growth-inhibiting activity of Tabebuia impetiginosa Martius ex DC dried inner bark-derived constituents against Helicobacter pylori ATCC 43504 was examined using paper disc diffusion and minimum inhibitory concentration (MIC) bioassays. The activity of the isolated compounds was compared to that of the commercially available anti-Helicobacter pylori agents, amoxicillin, metronidazole, and tetracycline. The biologically active components of Tabebuia impetiginosa dried inner bark (taheebo) were characterized by spectroscopic analysis as 2-(hydroxymethyl)anthraquinone, anthraquinone-2-carboxylic acid, and 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol). With the paper disc diffusion assay 2-(hydroxymethyl)anthraquinone exhibited strong activity against Helicobacter pylori ATCC 43504 at 0.01 mg/disc. Anthraquinone-2-carboxylic acid, lapachol and metronidazole were less effective, exhibiting moderate anti-Helicobacter pylori activity at 0.1 mg/disc. Amoxicillin and tetracycline were the most potent compounds tested, displaying very strong activity at 0.005 mg/disc. 2-(Hydroxymethyl)anthraquinone exhibited moderate activity at this dose. Tetracycline still had strong activity at 0.001 mg/disc while amoxicillin had little activity at this dose. In the MIC bioassay, 2-(hydroxymethyl)anthraquinone (2 microg/mL), anthraquinone-2-carboxylic acid (8 microg/mL), and lapachol (4 microg/mL) were more active than metronidazole (32 microg/mL) but less effective than amoxicillin (0.063 microg/mL) and tetracycline (0.5 microg/mL). The anti-Helicobacter pylori activity of seven 1,4-naphthoquinone derivatives (structurally related to lapachol), 1,4-naphthoquinone, 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin), 2-methyl-1,4-naphthoquinone (menadione), 2-hydroxy-1,4-naphthoquinone (lawsone), 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin), 5-hydroxy-1,4-naphthoquinone (juglone), and 2,3-dichloro-1,4-naphthoquinone (dichlone) was also evaluated using the paper disc assay. Menadione and plumbagin were the most potent compounds tested with the later still exhibiting very strong activity at 0.001 mg/disc. Menadione, juglone and tetracycline had strong activity at this low dose while the latter two compounds and amoxicillin had very strong activity at 0.005 mg/disc. Lawsone was unusual in that it had very strong activity at 0.1 and 0.05 mg/disc but weak activity at doses of 0.01 mg/disc and lower. Naphthazalin, lapachol and dichlone had similar activities while metronidazole had the lowest activity of all compounds tested. These results may be an indication of at least one of the pharmacological actions of taheebo. The Tabebuia impetiginosa dried inner bark-derived materials, particularly 2-(hydroxymethyl)anthraquinone, merit further study as potential Helicobacter pylori eradicating agents or lead compounds.     

Antibacterial, partially acetylated oligorhamnosides from Cleistopholis patens

Three new (1-3) and five known (4-8) partially acetylated oligorhamnoside derivatives were obtained from Cleistopholis patens via high-throughput natural products chemistry procedures. The rapid structure elucidation and dereplication were performed primarily utilizing a capillary-scale NMR probe and LR-/HRESIMS spectroscopic methods. Compounds 1, 2, and 6 were found to possess significant in vitro antibacterial activity against the Gram-positive bacteria methicillin-resistant Staphylococcus aureus ATCC 33591 and S. aureus 78-13607A with MICs of < or =16 microg/mL. Furthermore, 2 and 6 were found to show significant in vitro antibacterial activity against an expanded panel of Gram-positive pathogens including either ATCC strains or well-characterized clinical isolates from the global SENTRY Antimicrobial Surveillance Program.     

Inhibitors of osteoclast differentiation from Cephalotaxus koreana

Three new flavonoid glycosides ( 1- 3), 11-hydroxyhainanolidol ( 4), and a new dibenzylbutyrolactone lignan glycoside ( 5) were isolated from the aerial parts of Cephalotaxus koreana Nakai, along with 19 known flavonoids. The structures of the new compounds were elucidated using spectroscopic evidence, primarily NMR and MS. Twenty-four compounds were isolated, and among these isoscutellarein 5-O-beta-D-glucopyranoside ( 3), apigenin ( 6), kaempferol 3-O-alpha-L-rhamnopyranosyl(1'-->6')-beta-D-glucopyranoside ( 7), tamarixetin 3-O-alpha-L-rhamnopyranosyl(1'-->6')-beta-D-glucopyranoside ( 8), quercetin 3-O-[6'-O-acetyl]-beta-D-glucopyranoside ( 9), and quercetin 3-O-alpha-L-rhamnopyranoside ( 10) showed significant inhibitory activities against osteoclast differentiation at concentrations of 0.1 and 1.0 microg/mL.     

Prenylated flavonoids from the heartwood of Artocarpus communis with inhibitory activity on lipopolysaccharide-induced nitric oxide production

A new prenylated chalcone, 3' ',3' '-dimethylpyrano[3',4']2,4,2'-trihydroxychalcone (1), was isolated from the heartwood of Artocarpus communis. Two flavonoid derivatives, (-)-cycloartocarpin (9) and (-)-cudraflavone A (10), were isolated as new isomers. In addition, eight known flavonoids, isobacachalcone (2), morachalcone A (3), gemichalcones B (4) and C (5), artocarpin (6), cudraflavone C (7), licoflavone C (8), and (2S)-euchrenone a(7) (11), were isolated and identified from this plant for the first time. Compounds 1-4, 6, and 11 exhibited potent inhibitory activity on nitric oxide production in RAW264.7 LPS-activated mouse macrophage cells with IC(50) values of 18.8, 6.4, 16.4, 9.3, 18.7, and 12.3 microM, respectively. The structure of compound 1 was elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments.     

Gentisyl alcohol derivatives from the marine-derived fungus Penicillium terrestre

Nine new gentisyl alcohol derivatives, namely, the trimeric terrestrol A (8), dimeric terrestrols B-H (1-7), and a monomeric derivative (12), together with four known analogues (9-11, 13) were isolated from the marine-derived fungus Penicillium terrestre. The structures of the new compounds were elucidated by spectroscopic methods including one- and two-dimensional NMR as well as low- and high-resolution mass spectrometric analysis. These new compounds (1-8, 12) showed cytotoxic effects on HL-60, MOLT-4, BEL-7402, and A-549 cell lines with IC50 values in the range 5-65 microM. Compound 6 also showed moderate inhibitory activity against protein tyrosine kinases (Src and KDR). Furthermore, all new compounds exhibited moderate radical scavenging activity against DPPH with IC50 values in the range 2.6-8.5 microM.     

Microbial transformations of aryltetralone and aryltetralin lignans by Cunninghamella echinulata and Beauveria bassiana

Microbiological transformation of the aryltetralone lignan (-)-8'-epi-aristoligone (1) with Cunninghamella echinulata ATCC 10028B afforded two known natural lignans, (-)-holostyligone (3) and (-)-arisantetralone (4). Incubation of the aryltetralin lignan (-)-isogalbulin (2), obtained by chemical transformation of 1, with C. echinulata ATCC 10028B afforded the known lignan aryltetralol (5) and seven new metabolites, (-)-8-hydroxyisogalbulin (6), (-)-7-methoxyisogalbulin (7), (-)-4'-O-demethyl-8-hydroxyisogalbulin (8), (-)-7-methoxy-8-hydroxyisogalbulin (9), (-)-4'-O-demethyl-7-methoxyisogalbulin (10), (-)-4',5-O-didemethylcyclogalgravin (11), and (-)-4'-O-demethylcyclogalgravin (12). When 2 was subjected to biotransformation with Beauveria bassiana ATCC 7159, (-)-8-hydroxyisogalbulin (6) was the only isolable product. The structures of all new compounds were established by detailed analysis of their spectroscopic data.     

Anti-Helicobacter pylori compounds from Santalum album

Six new sesquiterpenes, (Z)-2beta-hydroxy-14-hydro-beta-santalol (1), (Z)-2alpha-hydroxy-albumol (2), 2R-(Z)-campherene-2,13-diol (3), (Z)-campherene-2beta,13-diol (4), (Z)-7-hydroxynuciferol (5), and (Z)-1beta-hydroxy-2-hydrolanceol (6), together with five known compounds, (Z)-alpha-santalol (7), (Z)-beta-santalol (8), (Z)-lanceol (9), alpha-santaldiol (10), and beta-santaldiol (11), were isolated from Santalum album, by using bioassay-guided fractionation for Helicobacter pylori. The structures were determined by extensive NMR studies. The absolute configuration of compound 3 was determined by a modified Mosher method. The crude extracts as well as the isolated compounds showed antibacterial activity against H. pylori. Especially, compounds 7 and 8 have strong anti-H. pylori activities against a clarithromycin-resistant strain (TS281) as well as other strains.     

Ingenamine G and cyclostellettamines G-I, K, and L from the new Brazilian species of marine sponge Pachychalina sp

The chemical investigation of the cytotoxic and antituberculosis active MeOH crude extract of the marine sponge Pachychalina sp. led to the isolation of six new nitrogenous metabolites, including ingenamine G (1), as well as a mixture of new cyclostellettamines G, H, I, K, and L (10-14) with the known cyclostellettamines A-F (4-9). Structural assignments of compound 1 were based on the analysis of MS and NMR data, while the structures of compounds 10-14 could be established by HPLC-MS/MS analysis. Ingenamine G displayed cytotoxic activity against HCT-8 (colon), B16 (leukemia), and MCF-7 (breast) cancer cell lines, antibacterial activity against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and four oxacilin-resistant S. aureus strains, and antimycobacterial activity against Mycobacterium tuberculosis H37Rv.     

New cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia membranacea

Bioassay-guided fractionation of an EtOAc-soluble extract of Casearia membranacea has resulted in the isolation of six new clerodane diterpenes, caseamembrins A-F (1-6), and a known compound, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (7). The structures of 1-6 were established on the basis of extensive 1D and 2D NMR spectroscopic analysis. In addition, the new derivatives, 8 and 9, were prepared by acylation of 7 and 3, respectively. The isolated diterpenoids and their derivatives were tested against human prostate (PC-3) and hepatoma (Hep3B) cancer cells. Compounds 1, 3-5, and 7 exhibited cytotoxicity against both tumor cells, with IC(50) values below 3 micromicro, while compounds 2, 6, 8, and 9 were less effective.     

Antibacterial diterpenes from the roots of Salvia blepharochlaena

The roots of Salvia blepharochlaena have yielded two new diterpenoids, blephaein (1) and O-methylpisiferic acid methyl ester (2), together with eight known diterpenoids. The structures of the new compounds were established by spectroscopic analysis and by some chemical reactions. Potent antibacterial activity was exhibited by the known compounds horminone (9) and 7-acetylhorminone (10) against Staphylococcus aureus ATCC 6538 P, Staphylococcus epidermidis ATCC 12226, and Bacillus subtilis ATCC 6633. Horminone was also found to be active against Enterococcus faecalis ATCC 29212.     

Cytotoxic cardiac glycosides and other compounds from Asclepias syriaca

Phytochemical investigation of the dried biomass of Asclepias syriaca afforded five new compounds (1-5), along with 19 known structures. Overall, the secondary metabolites isolated and identified from this plant showed a wide structural diversity including pentacyclic triterpenes, cardiac glycosides, flavonoid glycosides, lignans, a phenylethanoid, and a glycosylated megastigmane. In addition, the isolates were tested against the cancer breast cell line Hs578T, and those showing IC(50) values lower than 50 μM (1 and 6-9) were further investigated in three additional breast cancer cell lines (MCF-7, T47D, and Sk-Br-3) and the normal breast cell line Hs578Bst.     

Constituents of the stem bark of Pongamia pinnata with the potential to induce quinone reductase

Activity-guided fractionation of the petroleum ether and ethyl acetate extracts of the stem bark of Pongamia pinnata, using cultured Hepa 1c1c7 mouse hepatoma cells to evaluate quinone reductase (QR) inducing activity, led to the isolation of four new flavanone derivatives (1-4), one new flavone (5), one new chalcone (6), and 13 known compounds of the flavonoid, terpenoid, and fatty acid types. The structures of 1-6 were characterized on the basis of the interpretation of their spectroscopic data. The absolute stereochemistry of compounds 1-4 was determined from their CD data and by Mosher ester determination. All isolates obtained were evaluated in the quinone reductase induction assay.     

Isoflavone dimers and other bioactive constituents from the figs of Ficus mucuso

Phytochemical investigation of the figs of Ficus mucuso led to the isolation of three new isoflavone dimer derivatives, mucusisoflavones A-C (1-3), together with 16 known compounds. Some of the isolates were tested in vitro for their inhibitory properties toward β-glucuronidase and Plasmodium falciparum enoyl-ACP reductase (PfENR) enzymes. Compound 1 (IC??) 0.68 μM) showed inhibitory activity on β-glucuronidase enzyme, while 3 (IC??) 7.69 μM) exhibited a weak inhibitory activity against P. falciparum enoyl-ACP reductase (PfENR).     

Sesquiterpene lactones from Anthemis altissima and their anti-Helicobacter pylori activity

Seven sesquiterpene lactones, (-) sivasinolide (1), a new naturally occurring eudesmanolide (altissin, 2), desacetyl-beta-cyclopyrethrosin (3), tatridin-A (4), 1-epi-tatridin B (5), 1alpha,10beta-epoxy-6-hydroxy-1,10H-inunolide (6), and spiciformin (7), were isolated from Anthemis altissima. Also isolated were 10 known flavonoids, namely, apigenin (8), kaempferol 4'-methyl ether (9), quercetin (10), quercetin 3-methyl ether (11), isorhamnetin (12), rhamnetin (13), 6-hydroxyquercetin 3,6,4'-trimethyl ether (14), isoquercetrin (15), taxifolin (16), and eriodictyol (17), and one phenolic acid, chlorogenic acid (18). The structure and the stereochemistry of compound 2 were deduced by spectroscopic methods. The in vitro activity of the sesquiterpene lactones (1-5) against Helicobacter pylori, as well as against three Gram-positive and three Gram-negative bacteria growing aerobically, was tested using the microdilution method. Compounds 8-18 have also been tested against H. pylori.     

New isoprenylated flavones, artochamins A--E, and cytotoxic principles from Artocarpus chama

Five new isoprenylated flavones, artochamins A-E (1-5), together with eight known flavones (6-13), were isolated from the roots of Artocarpus chama. All structures were elucidated by spectroscopic methods. Artonin E (12) showed strong cytotoxicity against 1A9 (ovarian), significant activity against MCF-7 (breast adenocarcinoma), and moderate activity against HCT-8 (ileocecal) and MDA-MB-231 (breast adenocarcinoma) tumor cell lines. Artochamin C (3) was more potent against MCF-7, 1A9, HCT-8, and SK-MEL-2 (melanoma) than A549 (lung carcinoma), KB (epidermoid carcinoma of the nasopharynx), and its drug-resistant (KB-VIN) variant. Artocarpin (6) displayed weak but relatively broad inhibitory effects compared with 3 and 12.     

狭叶红景天的化学成分及其抑制结核分枝杆菌生长活性的研究

目的：研究狭叶红景天的化学成分；评价狭叶红景天提取物及其化学成分体外抗结核分枝杆菌(ATCC 27294) 活性。方法：运用硅胶，Sephadex LH-20，RP-18等柱色谱及半制备液相色谱对狭叶红景天的化学成分进行分离纯化，并利用核磁共振、质谱等技术，鉴定它们的化学结构；通过测试体外最低抑制浓度(minimal inhibitory concentrations, MIC) 和最低杀菌浓度(minimal bactericidal concentrations, MBC)来评价有关物质的抗结核分枝杆菌活性。结果：分离、纯化并鉴定了12个化合物，分别为β-谷甾醇(β-sitosterol,1)，酪醇(tyrosol,2)，反式-对羟基肉桂酸(trans-4-hydroxycinnamic acid,3)，香叶醇β-吡喃葡萄糖苷(geranyl-β-glucopyranoside,4)，橙花醇β-吡喃葡萄糖苷(neryl-β-glucopyranoside,5)，正己醇β-吡喃葡萄糖苷(hexyl β-glucopyranoside,6)，没食子酸(gallic acid,7)，表没食子儿茶素-3-没食子酸酯［(-)-epigallocatechin gallate,8］，棉皮素7-O-α-吡喃鼠李糖苷(rhodiolgin,9)，异落叶松树脂醇9-O-β-吡喃葡萄糖苷(isolariciresinol-9-O-β-glucopyranoside,10)，正辛醇α-吡喃阿拉伯糖(1→6)-β-吡喃葡萄糖苷(rhodiooctanoside,11)，和橙花醇α-吡喃阿拉伯糖(1→6)-β-吡喃葡萄糖苷(sacranoside B,12)。结论：化合物3,6,9～12为首次从狭叶红景天中发现，化合物4，5为首次从红景天属植物中分得；狭叶红景天80%乙醇提取物、醋酸乙酯萃取物以及化合物7，8，对结核分枝杆菌具有一定抑制和杀灭活性。     

Nitric oxide inhibitory substances from the rhizomes of Dioscorea membranacea

Thai medicinal plants locally known as Hua-Khao-Yen were examined for their inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cell lines. Among the plant species studied, an ethanolic extract of Dioscorea membranacea exhibited the most potent inhibitory activity, with an IC(50) value of 23.6 microg/ml. From this extract, eight compounds [two naphthofuranoxepins (1, 2), one phenanthraquinone (3), three steroids (4-6) and two steroidal saponins (7, 8)] were isolated and further investigated for their inhibitory properties of NO production. It was found that diosgenin-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-glucopyranoside (7) possessed the highest activity (IC(50)=3.5 microM), followed by dioscoreanone (3, IC(50)=9.8 microM) and dioscorealide B (2, IC(50)=24.9 microM). Regarding structural requirements of diosgenin derivatives for NO production inhibitory activity, compound 7 which has a rhamnoglucosyl moiety at C-3 exhibited much higher activity than compounds that have either a diglucosyl substitution (8) or its aglycone (9); whereas, hydroxyl substitution at position 8 of naphthofuranoxepin derivatives conferred higher activity than the methoxyl group. It is concluded that diosgenin-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-glucopyranoside (7), dioscoreanone (3) and dioscorealide B (2) are active principles for NO inhibitory activity of Dioscorea membranacea. Compounds 1-3 were also tested for the inhibitory effect on LPS-induced TNF-alpha release in RAW 264.7 cells. The result revealed that 3 possessed potent activity against TNF-alpha release with an IC(50) value of 17.6 microM, whereas, 1 and 2 exhibited mild activity. The present study may support the use of Dioscorea membranacea by Thai traditional doctors for treatment of the inflammatory diseases.     

Antibacterial anthraquinone derivatives from a sea anemone-derived fungus Nigrospora sp

Chemical investigation of a marine-derived fungus Nigrospora sp., isolated from an unidentified sea anemone, yielded two new hydroanthraquinone analogues, 4a-epi-9α-methoxydihydrodeoxybostrycin (1) and 10-deoxybostrycin (2), together with seven known anthraquinone derivatives (3-9). The structures of the two new compounds were established through extensive NMR spectroscopy as well as a single-crystal X-ray diffraction analysis using Cu Kα radiation. The antibacterial activities of compounds 1-9 and 10 acetyl derivatives (6a, 7a, 8a-8g, 9a) were evaluated in vitro. Compound 6a, the acetylated derivative of 6, exhibited promising activity against Bacillus cereus with an MIC value of 48.8 nM, which was stronger than that of the positive control ciprofloxacin (MIC = 1250 nM). Analysis of the antibacterial screening data for the metabolites and their acetyl derivatives revealed the key structural features required for this activity.     

Biocatalytic and antimetastatic studies of the marine cembranoids sarcophine and 2-epi-16-deoxysarcophine

The soft coral Sarcophyton glaucum is a rich resource of several bioactive cembranoids. Sarcophytol A (1) and sarcophine (2) are cembranoid diterpenes reported from this soft coral and extensively investigated for their cancer chemopreventive properties. This study aimed at investigating the antimetastatic potential of the major cembranoids, sarcophine (2) and 2-epi-16-deoxysarcophine (3), from the Red Sea soft coral S. glaucum. Biocatalytic transformation of 3 using Rhizopus stolonifer ATCC 6227a and Absidia spinosa ATCC 6648 afforded four new metabolites, 5-7 and 9, along with the known 9alpha-hydroxysarcophine (8). Sarcophine, 2-epi-16-deoxysarcophine, and metabolites 5-9 revealed significant antimetastatic activity against the highly metastatic mouse melanoma cell line (B16B15b). Cembranoids demonstrate a great potential for further development as antimetastatic agents.