A new antifungal and antiprotozoal depside from the Andean lichen Protousnea poeppigii

Extracts from the Andean lichens Protousnea poeppigii and Usnea florida displayed antimicrobial activity against the pathogenic fungi Microsporum gypseum, Trichophyton mentagrophytes and T. rubrum with MIC values between 50 and 100 microg/mL. From the active extracts, four main metabolites were isolated and identified as the new depside, isodivaricatic acid, and the known metabolites 5-propylresorcinol, divaricatinic acid and usnic acid. Isodivaricatic acid and divaricatinic acid presented antifungal effect towards M. gypseum with a MIC of 50 microg/mL and against T. mentagrophytes and T. rubrum and with MIC values of 50 and 100 microg/mL, respectively. The new isodivaricatic acid was active towards Leishmania amazonensis, Leishmania brasiliensis and Leishmania infantum promastigotes with 100% lysis at 100 microg/mL.The activity of the new compound decreased on acetylation of the hydroxy groups as well as on methylation of the acid function. The structures were elucidated by spectroscopic means. The spectroscopic data of isodivaricatic acid are presented here for the first time.     

Phenolic glycosides from Dirca palustris

Five novel phenolic glycosides (1-5) were isolated from the MeOH extract of the dried twigs of Dirca palustris, as confirmed by their (1)H NMR, (13)C NMR, and MS data. Compounds 1-3 were not active against cyclooxygenase I (COX-I), but compound 4 (200 microg/mL) and compound 5 (125 microg/mL) showed 12.5 and 9.2% inhibition of the COX-I enzyme, respectively. Compounds 1-5 did not exhibit cyclooxygenase II (COX-II) enzyme inhibition. Compound 5 did not show any antioxidant activity using the liposome assay; however, compounds 1-4 displayed antioxidant activity at 60 microg/mL, with compound 2 being the most efficacious.     

New sesquiterpenoids from the root of Guatteria multivenia

A phytochemical investigation of the CHCl(3) fraction of an ethanol extract of the root of Guatteria multivenia furnished nine compounds, of which four are sesquiterpenes (1-4) and five are alkaloids (5-9). Of the four sesquiterpenes, two are new (1, 3), named guatterin A (1) and dihydromadolin-K (3), and two are known (2, 4), identified as madolin-K (2) and madolin-W (4). The five known alkaloids were identified as liriodenine (5), lysicamine (6), lanuginosine (7), guadiscine (8), and O-methylpallidine (9). All the known compounds were isolated from this species for the first time. Structures of the new compounds were determined by extensive NMR studies, including DEPT, COSY, HMQC, HMBC, and NOESY. Compound 7 showed weak inhibitory effect against Candida albicans secreted aspartic proteases (SAP) with IC(50) of 45 microg/mL. Compound 5 was found to have antimicrobial activity against C. albicans, Cryptococcusneoformans, Staphylococcus aureus, and methicillin-resistant S. aureus (MRS) with IC(50)/MIC values of 3.5/6.25, 2.0/12.5, 2.0/3.13, and 2.0/3.13 microg/mL, respectively.     

Antibacterial compounds from Planchonia careya leaf extracts

AIM OF THE STUDY: The leaves of Planchonia careya (F. Muell.) R. Knuth (Lecythidaceae) have been traditionally implemented in the treatment of wounds by the indigenous people of northern Australia, although the compounds responsible for the medicinal properties have not been identified. In this study, antibacterial compounds from the leaf extracts were isolated and characterized, and the biological activity of each compound was assessed. MATERIALS AND METHODS: Compounds were isolated from the leaf extracts using HPLC-piloted activity-guided fractionation. The minimum inhibitory concentrations (MICs) were assessed with plate-hole diffusion assays, and the cytotoxicity was determined with MTT assays using monkey kidney epithelial (MA104) cells. RESULTS: Six known compounds were isolated from the leaf extracts and were identified as 1, (+)-gallocatechin; 2, gallocatechin-(4alpha-->8)-gallocatechin; 3, 9(S)-hydroxy-10E,12Z-octadecadienoic acid (alpha-dimorphecolic acid); 4, 2alpha,3beta,24-trihydroxyolean-12-en-28-oic acid (hyptatic acid-A); 5, 3beta-O-cis-p-coumaroyltormentic acid; and 6, 3beta-O-trans-p-coumaroyltormentic acid. Compounds 5 and 6 were weakly selective for vancomycin-resistant Enterococcus (VRE) compared with eukaryotic cells, with an MIC of 59.4microg/mL and a 50% inhibitory concentration (IC(50)) of 72.0microg/mL for MA104 cells. CONCLUSIONS: The isolation of six antibacterial compounds from the leaves of Planchonia careya validates the use of this species as a topical wound-healing remedy.     

Cacofurans A and B, new furanoditerpenes from a marine sponge.

Two new labdane-class diterpenes, cacofurans A (1) and B (2), have been isolated from a sponge Cacospongia sp. Their structures were determined by analyzing spectroscopic data, by chemical transformations, and by X-ray diffraction. Cacofurans 1 and 2 inhibited the development of fertilized sea urchin eggs at concentrations of 0.5 and 5 microg/mL and showed an actin-disrupting effect on the NBT-II cell line at 10 microg/mL.     

Chlorohydroaspyrones A and B, antibacterial aspyrone derivatives from the marine-derived fungus Exophiala sp

Chlorohydroaspyrones A (1) and B (2), antibacterial aspyrone derivatives, and the previously described aspyrone (3), asperlactone (4), and penicillic acid (5) have been isolated from the broth of a marine isolate of the fungus Exophiala. The structure and absolute stereochemistry of the compounds were determined on the basis of the physicochemical data analysis and chemical reactions. Compounds 1 and 2 exhibited a mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values of each strain are as follows: compound 1 showed 62.5 microg/mL for S. aureus and 125 microg/mL for methicillin-resistant S. aureus and multidrug-resistant S. aureus, and compound 2, 62.5 microg/mL for S. aureus and methicillin-resistant S. aureus and 125 microg/mL for multidrug-resistant S. aureus.     

Daucane sesquiterpenes from Ferula hermonis

The roots of Ferula hermonis Boiss yielded two new daucane esters, 14-(4'-hydroxybenzoyloxy)dauc-4,8-diene (1) and 14-(4'-hydroxy-3'-methoxybenzoyloxy)dauc-4,8-diene (2), together with the four known sesquiterpenes jaeschkeanadiol p-hydroxybenzoate (3), jaeschkeanadiol benzoate (4), jaeschkeanadiol (5), and epoxyjaeschkeanadiol (6). The identities of the isolated compounds were ascertained primarily using NMR and MS data. Compounds 1 and 3 exhibited antimicrobial activity against Staphylococcus aureus with IC(50) 1.5 and 3.5 microg/mL, respectively, and against Methicillin-resistant S. aureus with IC(50) 2.0 and 4.0 microg/mL, respectively.     

Isolation and identification of cytotoxic compounds from the wood of Pinus resinosa

Methanol extracts of wood from Pinus resinosa were found to be selectively cytotoxic against human lung carcinoma cells, A549 (IC50 41 +/- 6 microg/mL), human colorectal adenocarcinoma cells, DLD-1 (IC50 47 +/- 4 microg/mL) in comparison with healthy cells, WS1 (IC50 130 +/- 11 microg/mL). Five known compounds were isolated and identified by 1H, 13C NMRspectroscopy and HR-ESI-MS mass spectrometry as, pinosylvin monomethyl ether (1), pinosylvin (2), pinosylvin dimethyl ether (3), pinobanksin (4) and (-)-norachelogenin (5). Compound 4 was isolated for the first time in P. resinosa. The cytotoxicity of compounds 1-5 was evaluated against A549, DLD-1 and WS1. Compound 1 exhibited the strongest cytotoxicity against both tumor cell lines and the healthy cell line with an IC50 of 25 +/- 4 microm for A549, 20 +/- 1 microm for DLD-1 and 34 +/- 3 microm for WS1.     

Antibacterial activity of [10]-gingerol and [12]-gingerol isolated from ginger rhizome against periodontal bacteria

Ginger (Zingiber officinale Roscoe) has been used widely as a food spice and an herbal medicine. In particular, its gingerol-related components have been reported to possess antimicrobial and antifungal properties, as well as several pharmaceutical properties. However, the effective ginger constituents that inhibit the growth of oral bacteria associated with periodontitis in the human oral cavity have not been elucidated. This study revealed that the ethanol and n-hexane extracts of ginger exhibited antibacterial activities against three anaerobic Gram-negative bacteria, Porphyromonas gingivalis ATCC 53978, Porphyromonas endodontalis ATCC 35406 and Prevotella intermedia ATCC 25611, causing periodontal diseases. Thereafter, five ginger constituents were isolated by a preparative high-performance liquid chromatographic method from the active silica-gel column chromatography fractions, elucidated their structures by nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry and their antibacterial activity evaluated. In conclusion, two highly alkylated gingerols, [10]-gingerol and [12]-gingerol effectively inhibited the growth of these oral pathogens at a minimum inhibitory concentration (MIC) range of 6-30 microg/mL. These ginger compounds also killed the oral pathogens at a minimum bactericidal concentration (MBC) range of 4-20 microg/mL, but not the other ginger compounds 5-acetoxy-[6]-gingerol, 3,5-diacetoxy-[6]-gingerdiol and galanolactone.     

Anthelmintic macrolactams from Nonomuraea turkmeniaca MA7364

Two new macrolactams, 6-desmethyl-N-methylfluvirucin A1 (1) and N-methylfluvirucin A1 (2), have been isolated from the acetone extract of Nonomuraea turkmeniaca MA7364. These compounds were isolated by bioassay-guided fractionation as part of our search for new anthelmintics. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported fluvirucins and confirmed by 2D NMR. Compound 1 exhibited in vitro activity (EC(90) 15 +/- 5 microg/mL) against Haemonchus contortus larvae, whereas compound 2, while a bit less active in vitro (EC(90) 29 +/- 8 microg/mL), showed modest in vivo activity against a surrogate organism, Heligmosomoides polygyrus in mice, at 50 mg/kg.     

Cytotoxic diterpenoids from the soft coral Sarcophyton crassocaule

Five new cembrane diterpenoids, sarcrassins A-E (1-5) along with a known compound, emblide (6), have been isolated from the soft coral Sarcophyton crassocaule collected from the Bay of Sanya, Hainan Island, China. The structures of 1-5 were determined by spectroscopic methods including 1D and 2D NMR techniques. Their relative configurations were determined by NMR data and NOESY experiments. Compounds 2, 4, and 6 exhibited significant cytotoxic activities against KB cell lines with IC50 values of 5.0, 4.0, and 5.0 microg/mL, respectively, while compounds 1 and 5 showed moderate cytotoxicity toward KB cell lines with IC50 values of 19.0 and 13.0 microg/mL, respectively.     

Antifouling activity of meroditerpenoids from the marine brown alga Halidrys siliquosa

Nine tetraprenyltoluquinol-related metabolites (1-9) have been isolated from the organic extract of the temperate brown alga Halidrys siliquosa that exhibits antifouling properties. The planar structure of compounds 1-9 was elucidated on the basis of extensive spectroscopic analysis and by comparison of the data with those of related metabolites. Antifouling and toxicity tests were conducted on these compounds: the most active (compounds 2, 6, and 9) inhibited both the growth of four strains of bacteria (MICs < 2.5 microg/mL) and settlement of cyprids of Balanus amphitrite (EC50 < 5 microg/mL), the latter at nontoxic concentrations (LC50 > 5 microg/mL).     

Phrygiasterol, a cytotoxic cyclopropane-containing polyhydroxysteroid, and related compounds from the pacific starfish Hippasteria phrygiana

The new cyclopropane-containing steroid phrygiasterol (1) and steroid glycoside phrygioside B (2), along with previously known borealoside C (2a) and (20R,24S)-5alpha-cholesta-3beta,6alpha,8,15alpha,24-pentaol (3), have been isolated from the Pacific starfish Hippasteria phrygiana. On the basis of spectroscopic analyses, using 1D and 2D NMR techniques and some chemical transformations, the structures of 1 and 2 have been established as (20R,24R,25R)-24,26-cyclo-5alpha-cholesta-3beta,6alpha,8,15alpha,16beta,27-hexaol (1) and the sodium salt of (20R,24S)-24-O-(3-O-methyl-4-O-sulfate-beta-d-xylopyranosyl)-5alpha-cholesta-3beta,6alpha,8,15alpha,24-pentaol (2), respectively. Compound 1 inhibited the growth of Ehrlich carcinoma cells with an IC(50) of 50 microg/mL, whereas 2 induced apoptosis of the same cells (EC(50)=70 microg/mL) and inhibited Ca(2+) influx into mouse spleenocytes (EC(50)=20microg/mL).     

New bioactive peroxides from marine sponges of the family plakiniidae

In our continuing program to identify compounds with antifungal properties, the ethanol extracts of two sponges of the family Plakinidae were found to inhibit the growth of the fungal pathogens Candida albicans and Aspergillus fumigatus. From these organisms three new compounds and five known compounds have been identified. A new 1,2-dioxane ring peroxide acid, 1, has been isolated from the sponge Plakortis halichondrioides along with five known compounds. Two new 1,2-dioxolane peroxide acids, 3 and 4, have been isolated from the sponge Plakinastrella onkodes. The structures were established by interpretation of spectral data. The three new compounds exhibit moderate activity against the fungal pathogen C. albicans with MICs of 5, 1.6, and 1.6 microg/mL respectively, for 1, 3, and 4. Compound 1 also showed in vitro inhibition of the fungal pathogen A. fumigatus with an IC(90) value of 5.6 microg/mL.     

Antibacterial activity of two canthin-6-one alkaloids from Allium neapolitanum

The emergence of multidrug-resistant strains of many human pathogens has led to an urgent need for the discovery and development of new antimicrobial agents. As part of an ongoing investigation into the antibacterial properties of the Alliaceae, the isolation of 1 (canthin-6-one), 2 (8-hydroxy-canthin-6-one) and 3 (5(zeta)-hydroxy-octadeca-6(E)-8(Z)-dienioc acid)) from A. neapolitanum, a perennial bulbous herb found in open pastures of the Mediterranean is reported. Compounds 1 and 2 were isolated by Sephadex LH-20 from fractions exhibiting a positive reaction with Dragendorff's reagent on TLC, compound 3 was isolated after HPLC purification of Sephadex fractions. Structures were elucidated by extensive 1D and 2D NMR experiments and are in accordance with published data, however, the 13C NMR data for compound 2 and the 1H and 13C NMR data for compound 3 are reported here for the first time. Canthin-6-one alkaloids are well-known constituents of the Simaroubaceae and Rutaceae, and display a wide range of biological activities. These metabolites are reported as constituents of the Alliaceae here for the first time, and displayed minimum inhibitory concentrations (MICs) in the range 8-32 microg/mL against a panel of fast-growing Mycobacterium species and 8-64 microg/mL against multidrug-resistant (MDR) and methicillin-resistant (MRSA) strains of Staphylococcus aureus. Compound 3 displayed antimycobacterial activity in the range of 16-32 microg/mL.     

三列凹顶藻化学成分研究 Ⅱ

目的：从三列凹顶藻Laurencia tristicha中寻找具有多样性结构的化学成分,供药理活性筛选。方法：采用凝胶柱色谱、硅胶柱色谱、重结晶和高效液相色谱等方法进行分离；借助核磁共振等波谱方法鉴定化合物的结构；用MTT法对得到的化合物进行细胞毒活性评价。结果：分离得到7个化合物,分别鉴定为鉴定为胆甾醇(1),胆甾-5-烯-3β,7α二醇(2),β-谷甾醇(3),叶绿醇(4),玉米黄素(5),对羟基苯甲醛(6),3-吲哚甲醛(7)；在人肿瘤细胞株HCT-8,Bel-7402,BGc-823,A549和HELA模型上,化合物2对所有细胞株均显示毒性,化合物4对HCT-8和HELA细胞显示中等强度的细胞毒活性,其它化合物对所有细胞株均无明显毒性,IC₅₀均大于100 μg·mL^-1。结论：化合物1～7均为首次从三列凹顶藻中得到,化合物2对所有细胞株均显示毒性,化合物4对HCT-8和HELA细胞具有中等强度的选择性细胞毒活性。     

Wound healing activity of acylated iridoid glycosides from Scrophularia nodosa.

Three acylated iridoid glycosides (E)-6-O-(2", 4"-diacetyl-3" -O-p-methoxycinnamoyl)-alpha-L-rhamnopyranosyl catalpol (scopolioside A) (1), (E)-6-O-(2"-acetyl-3", 4"-di-O,O-p-methoxycinnamoyl)-alpha-L-rhamnopyranosyl catalpol (scrophuloside A(4)) (2) and (E)-6-O-(2",3"-diacetyl-4"-O-p-methoxycinnamoyl)-alpha-L-rhamnopyranosyl catalpol (scrovalentinoside) (3) have been isolated from the dried seed pods of Scrophularia nodosa by HPLC. Their structures were determined by 1D and 2D NMR, UV/Vis and mass spectroscopy and by comparison with published data. All three compounds were shown in vitro to stimulate the growth of human dermal fibroblasts. The effect was negatively dose-dependent for 2 and 3 for which fibroblast growth stimulation was highest at 0.78 microg/mL but was not significantly different from the control at 100 microg/mL. The presence of these compounds in the mature seed pods may explain the ethnobotanical use of this plant in Europe for healing wounds.     

Cyclopentenones, scaffolds for organic syntheses produced by the endophytic fungus mitosporic dothideomycete sp. LRUB20

Two new natural products, 2-hydroxymethyl-3-methylcyclopent-2-enone (1) (synthetically known) and cis-2-hydroxymethyl-3-methylcyclopentanone (2), and a known compound, asterric acid (3), were isolated from the endophytic fungus mitosporic Dothideomycete sp. LRUB20, which was isolated from the stem of the Thai medicinal plant Leea rubra. Compound 2 was separated and identified in the form of its 2,4-dinitrophenylhydrazone derivative (5). Compounds 1, 3, and hydrazone 5 exhibited mild antimycobacterial activity, both with MIC values of 200 microg/mL. Compounds 1, 3, and 4 were inactive (at 50 microg/mL) toward Vero, KB, NCI-H187, and BC cell lines. Hydrazone 5 showed only mild cytotoxicity against the Vero cell line with an IC(50) value of 21.7 microg/mL; however, it was inactive toward KB, NCI-H187, and BC cell lines. Endophytic fungi may be a source for the production of building blocks for organic syntheses.     

Potent antiviral potamogetonyde and potamogetonol, new furanoid labdane diterpenes from Potamogeton malaianus

New furanoid labdane diterpenes, potamogetonyde (3) and potamogetonol (4), together with two known compounds, potamogetonin (1) and 15,16-epoxy-12-oxo-8(17),13(16),14-labdatrien-20,19-olide (2), were isolated from the CH(2)Cl(2) extract of Potamogeton malaianus. The chemical structures of 1-4 were elucidated by the analyses of their spectral data, mainly by 1D and 2D NMR techniques. Potamogetonyde (3) and potamogetonol (4) exhibited potent antiviral (HSV-1) activity with respective IC(50) values of 8 and 3 microg/mL. Compounds 1-4 possessed cytotoxicity toward insect cells (fall armyworm and mosquito larvae, IC(50) of 11-72 microg/mL). Furanoid diterpenes 3 and 4 also exhibited cytotoxicity against the Vero cell line with respective IC(50)'s of 31 and 28 microg/mL, while 1 and 2 were inactive at 50 microg/mL. Compounds 1-4 were inactive (at 20 microg/mL) against KB and BC cell lines and showed only weak antimycobacterial activity against Mycobacterium tuberculosis H37Ra with minimum inhibitory concentrations of 50-100 microg/mL.