Benzoylphloroglucinol derivatives from Hypericum scabrum

Nine new polyprenylated benzoylphloroglucinol derivatives, hyperibones A-I (1-9), were isolated from the aerial parts of the Uzbekistan medicinal plant Hypericum scabrum. Their structures were determined mainly on the basis of spectroscopic evidence (2D NMR and HRMS). Compounds 1, 2, and 4 showed mild in vitro antibacterial activity against methicillin-resistance Staphylococus aureus (MRSA) and methicillin-sensitive Staphylococus aureus (MSSA).     

Antimicrobial metabolites from the Paracel Islands sponge Agelas mauritiana

Four new alkaloids, (-)-8'-oxo-agelasine D (2), ageloxime B (3), (+)-2-oxo-agelasidine C (4), and 4-bromo-N-(butoxymethyl)-1H-pyrrole-2-carboxamide (5), and the known compound (-)-ageloxime D (1) were isolated from the marine sponge Agelas mauritiana. Their chemical structures were established on the basis of spectroscopic analysis. Compounds 1 and 3 both showed antifungal activity against Cryptococcus neoformans and antileishmanial activity against Leishmania donovani in vitro. Compound 3 also exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureusin vitro.     

The antibacterial ent-eusynstyelamide B and eusynstyelamides D, E, and F from the Arctic bryozoan Tegella cf. spitzbergensis

The brominated tryptophan-derived ent-eusynstyelamide B (1) and three new derivatives, eusynstyelamides D, E, and F (2-4), were isolated from the Arctic bryozoan Tegella cf. spitzbergensis. The structures were elucidated by spectroscopic methods including 1D and 2D NMR and analysis of mass spectrometric data. The enantiomer of 1, eusynstyelamide B, has previously been isolated from the Australian ascidian Eusynstyela latericius. Antimicrobial activities are here reported for 1-4, with minimum inhibitory concentrations (MIC) as low as 6.25 μg/mL for 1 and 4 against Staphylococcus aureus. Eusynstyelamides 2 and 3 showed weak cytotoxic activity against the human melanoma A 2058 cell line.     

Labdane and kaurane diterpenoids from Plectranthus fruticosus

Six new diterpenoids, three labdane and three kaurane derivatives, have been isolated from an acetone extract of Plectranthus fruticosus together with other already known substances. The structures of these compounds (1-5 and 7) were established mainly by spectroscopic means, particularly by 1D and 2D NMR studies, as well as by some chemical correlations with known diterpenoids. The physical and spectroscopic data of the derivative 11, obtained by hydrolysis of the labdane 2, were identical to those reported for a compound previously isolated from Croton joufra, to which structure 12 had been established erroneously by other authors. Several of the isolated compounds were tested as antimicrobial agents against three bacteria strains and one yeast strain, but only 4 showed a moderate inhibitory activity against Staphylococcus aureus.     

Antibacterial polyketides from the jellyfish-derived fungus Paecilomyces variotii

Four new polyketides (1-4) were isolated from the fungus Paecilomyces variotii, which was derived from the jellyfish Nemopilema nomurai. The planar structures and relative configurations of these polyketides were elucidated on the basis of spectroscopic analyses, including 2D NMR experiments. The compounds showed inhibitory activity against pathogenic bacteria including methicillin-resistant Staphylococcus aureus 3089 and multi-drug-resistant Vibrio parahemolyticus 7001 with MIC values in the range 5-40 μg/mL.     

Antimicrobial triterpenoids from Vladimiria muliensis

A new triterpenoid with a rearranged ursane skeleton, 3beta-acetoxyl-11alpha-methoxybauer-8-en-7alpha-ol ( 1), two new ursane triterpenoids, 1alpha,5alpha-dioxy-11alpha-hydroxyurs-12-en-3-one ( 2) and urs-3beta,13alpha,18beta-triol ( 3), together with three known ursane triterpenoids ( 4- 6) were isolated from the rhizome of Vladimiria muliensis. Their structures were elucidated on the basis of spectroscopic methods (IR, EIMS, HRESIMS, 1D and 2D NMR, and X-ray crystallography diffraction). Compounds 2 and 4 exhibited modest antimicrobial activity against Escherichia coli, Candida albicans, Pseudomonas aeruginosa, Enterococcus faecalis, Bacillus cereus, and Staphylococcus aureus.     

Antimicrobial cuparene-type sesquiterpenes, enokipodins C and D, from a mycelial culture of Flammulina velutipes

Two new cuparene-type sesquiterpenes, enokipodins C (1) and D (2), were isolated from culture medium of an edible mushroom, Flammulina velutipes, along with enokipodins A (3) and B (4). The structures of 1 and 2 were determined using spectroscopic methods (HRMS, (1)H and (13)C, and 2D NMR). The absolute configuration of enokipodin C was determined from the observed (1)H NMR chemical shifts and NOEs in NOESY experiments after conversion into the corresponding esters with the chiral reagent 2-(2'-methoxy-1'-naphthyl)-3,4-dichlorobenzoic acid. All the metabolites showed antimicrobial activity against a fungus, Cladosporium herbarum, and Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus.     

Sesquiterpenoids from Artemisia gilvescens and an anti-MRSA compound

A new secoguaianolide sesquiterpene (1) was isolated along with its three stereoisomers (2-4) from the nonmedicinal plant Artemisia gilvescens. The structure of 1 was elucidated to be (4S,5S)-dihydro-5-[(1R,2S)-2-hydroxy-2-methyl-5-oxo-3-cyclopenten-1-yl]-3-methylene-4-(3-oxobutyl)-2(3H)-furanone on the basis of 2D NMR and other spectroscopic evidence. Five known sesquiterpenoids were also isolated from this plant, and one of them (5) showed activity against methicillin-resistant Staphylococcus aureus (MRSA).     

Sorocenols G and H, anti-MRSA oxygen heterocyclic Diels-Alder-type adducts from Sorocea muriculata roots

Bioassay-guided fractionation of a root extract of Sorocea muriculata led to the isolation and identification of two new oxygen heterocyclic Diels-Alder-type adducts, sorocenols G (1) and H (2), along with lupeol-3-(3' R-hydroxytetradecanoate) and oxyresveratrol. The structures of 1 and 2 were elucidated using 1D and 2D NMR spectroscopic and HRMS data and by comparison with reported values. The absolute configurations of 1 and 2 were established by analysis of their experimental and theoretically calculated CD spectra. Compounds 1 and 2 showed significant and selective activity against methicillin-resistant Staphylococcus aureus with IC50 values of 1.5 and 0.5 microM, respectively. Compound 2 also displayed antifungal activity against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, with IC 50 values of 5.4, 5.4, and 10.0 microM, respectively.     

New polyoxygenated farnesylcyclohexenones, deacetoxyyanuthone A and its hydro derivative from the marine-derived fungus Penicillium sp

New polyoxygenated farnesylcyclohexenones, 7-deacetoxyyanuthone A (1) and its 2,3-hydro derivative (2), were isolated together with the known farnesylquinones (3, 4) from a marine isolate of the genus Penicillium. The structures of the new deacetoxyyanuthone A (1) and its 2,3-hydro derivative (2) were assigned by spectroscopic methods, including 2D NMR and CD for the Cotton effect of alpha-epoxyketone experiments. Compounds 1 and 3 showed moderate in vitro cytotoxicity in a panel of five human tumor cell lines, and 1 also exhibited mild in vitro antibacterial activity against methicillin-resistant and multidrug-resistant Staphylococcus aureus (MIC, 50 microg/mL).     

New antimicrobial filicinic acid derivatives from Hypericum drummondii.

Bioactivity-guided fractionation of the hexane extract of the stems and leaves of Hypericum drummondii has afforded four new filicinic acid derivatives: drummondin D, isodrummondin D, drummondin E, and drummondin F. The structures of these compounds were established by spectroscopic methods. All compounds possessed strong antibiotic activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis and the acid fast bacterium Mycobacterium smegmatis.     

Induced production of bromomethylchlamydosporols A and B from the marine-derived fungus Fusarium tricinctum

The addition of CaBr(2) to the fermentation of a marine-derived Fusarium tricinctum resulted in production of halogenated chlamydosporol analogues. Two new antimicrobial halogenated pyranopyranones, bromomethylchlamydosporols A (1) and B (2), and two known compounds, chlamydosporol (an inseparable epimeric mixture of 7R:7S = 1:1 from (1)H NMR data) (3) and fusarielin A (4), were isolated from the culture. The structures of 1 and 2 were assigned through a combination of spectroscopic data analyses. Compounds 1-4 exhibited mild antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC values of each strain were as follows: compounds 1 and 2 showed an MIC of 15.6 μg/mL against S. aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus, and compounds 3 and 4 exhibited an MIC of 31.5 μg/mL against S. aureus and methicillin-resistant S. aureus and 62.5 μg/mL against multidrug-resistant S. aureus.     

Antibacterial activity of labdane diterpenoids from Stemodia foliosa

As part of a continuing interest in exploring the chemistry of Brazilian medicinal plants, three new labdane diterpenoids, 6alpha-acetoxymanoyl oxide (1), 6alpha-malonyloxymanoyl oxide (2), and 6alpha-malonyloxy-n-butyl ester manoyl oxide (3), together with the known betulinic acid, lupeol, sitosterol, and stigmasterol, were isolated from the aerial parts of Stemodia foliosa. The structures of 1-3 were established on the basis of interpretation of spectroscopic data, including HRESIMS, and 1D and 2D NMR techniques. All compounds were tested against a bacteria panel consisting of Staphylococcus aureus, Bacillus cereus, B. subtilis, B. anthracis, Micrococcus luteus, Mycobacterium smegmatis, and M. phlei. Compound 2 showed moderate activity against these strains, with MIC values in the range 7-20 microg/mL.     

5-methylcoumaranones from Mutisia friesiana and their bioactivity

In addition to the known mutisicoumaranones A (1) and B (2), the methanolic extract of the aerial parts of the shrub Mutisia friesiana afforded two new 5-methylcoumaranones, mutisicoumaranones C (3) and D (4). Their structures were elucidated by spectroscopic methods. (13)C NMR data for mutisicoumaranones A and B are reported for the first time. All compounds showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum and bactericidal activity against Staphylococcus aureus. The presence of 5-methylcoumaranones A-D is biosynthetically related to 5-methylcoumarins and phenolic derivatives previously isolated from M. friesiana.     

Brominated diterpenes with antibacterial activity from the red alga Sphaerococcus coronopifolius

Four new brominated diterpenes (1, 2, 4, 5), along with two previously reported metabolites (3, 6), were isolated from the organic extract of Sphaerococcus coronopifolius, collected in Palaiokastritsa Bay at the west coast of Corfu Island. The structures of the new products, as well as their relative configuration, were established by means of spectroscopic data analyses, including 2D NMR experiments. The isolated metabolites were evaluated for their antibacterial activity against a panel of multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA) with MICs in the range 0.5-128 microg/mL.     

Oleanane-type triterpenes from the flowers and roots of Saussurea muliensis

Six new oleanane-type triterpenes (1- 6), along with five known compounds, were isolated from the flowers and roots of Saussurea muliensis. On the basis of spectroscopic methods, with special emphasis on 1D and 2D NMR techniques, the structures of the new compounds were characterized as 3beta,22alpha-dihydroxyolean-12-en-30-oic acid (1), 3alpha-(E)-caffeoyloxyolean-12-en-30-oic acid (2), 3alpha-(E)-coumaroyloxyolean-12-en-30-oic acid (3), 3alpha,22alpha-diacetoxy-20beta,21alpha,29-trihydroxy-30-norolean-12-ene (4), 3alpha,22alpha-diacetoxy-21alpha,29-dihydroxy-20beta-methoxy-30-norolean-12-ene (5), and 3alpha,22alpha-diacetoxy-20beta,21alpha-dihydroxy-29-palmityloxy-30-norolean-12-ene (6). The isolated compounds (1- 6) were not active against Staphylococcus aureus, Escherichia coli, Bacillus cereus, and Candida albicans.     

A novel antibacterial iridoid and triterpene from Caiophora coronata

Bioassay-guided fractionation of the antibacterial CH(2)Cl(2)-MeOH extract obtained from the aerial parts of the Argentinean plant Caiophora coronata led to the isolation of a new triterpene, 1beta,3beta-dihydroxyurs-12-en-27-oic acid, 1, and a new iridoid, 1alpha-methoxy-6alpha,10-dihydroxyisoepiiridomyrmecin (caiophoraenin), 2, along with the known iridoid isoboonein 3. Their structures were established by spectroscopic techniques (1D and 2D NMR, HRFABMS, FTIR). The MIC values of isolated compounds were determined against methicillin-sensitive (MSSA) and -resistant (MRSA) strains of Staphylococcus aureus, Bacillus subtilis (BS), vancomycin-resistant Enterococcus faecium (VREF), Escherichia coli (EC), E. coli imp (ECimp), and Candida albicans (CA). Compound 1 was found active against BS, MSSA, MRSA, VREF, and ECimp with MIC values of 2, 4, 4, 4, and 16 microg/mL, respectively.     

5-alkylresorcinols from Merulius incarnatus

Two new, 5-heptadeca-8'Z,11'Z,16-trienylresorcinol (1) and 5-heptadeca-9'E,11'Z,16-trienylresorcinol (2), and six known 5-alkylresorcinols (3-8) were isolated from the mushroom Merulius incarnatus. Compound 2 is the first 5-alkylresorcinol derivative that contains a trans-cis conjugated double bond system. Compounds 1, 2, 5, 6, 7, and 8 were found to inhibit methacillin-resistant Staphylococcus aureus (MRSA) with IC(50) values of 2.5, 15, 9.5, 8.0, 5.0, and 6.5 microg/mL, respectively. Compound 1 was also active against leishmania, with an IC(50) value of 3.6 microg/mL, and showed no cytotoxicity in our Vero cell test up to a concentration of 25 microg/mL. The structures of these isolates were determined by spectroscopic data including 1D and 2D NMR.     

Isolation and bioactivities of constitutents of the roots of Garcinia atroviridis

Two new prenylated compounds, the benzoquinone atrovirinone (1) and the depsidone atrovirisidone (2), were isolated from the roots of Garcinia atroviridis. Their structures were determined on the basis of the analysis of spectroscopic data. While compound 2 showed some cytotoxicity against HeLa cells, both compounds 1 and 2 were only mildly inhibitory toward Bacillus cereus and Staphylococcus aureus.     

Norlignans, acylphloroglucinols, and a dimeric xanthone from Hypericum chinense

Two new norlignans, hyperiones A (1) and B (2), three new acylphloroglucinols, aspidinol C (3) and hyperaspidinols A (5) and B (6), the known compound aspidinol D (4), and the symmetrical dimeric xanthone hyperidixanthone (7) were isolated from Hypericum chinense. Their structures were established by spectroscopic analysis. In an antibacterial assay using a panel of multidrug-resistant (MDR) strains, compounds 3 and 4 exhibited promising activity against the NorA efflux protein overexpressing MDR Staphylococcus aureus strain SA-1199B with a minimum inhibitory concentration (MIC) of 2 μg/mL (8.4 μM) and 4 μg/mL (16.8 μM), respectively. The positive control antibiotic norfloxacin showed activity at MIC 32 μg/mL (100 μM).