Gerronemins A-F, cytotoxic biscatechols from a Gerronema species

The gerronemins A-F (1-6) were isolated as the cytotoxic components of an extract of a Gerronema species detected in a screening for new cytotoxic metabolites from basidiomycetes. Their structures were elucidated by spectroscopic techniques, and they are composed of a C12-C16 alkane or alkene substituted at both ends by 2,3-dihydroxyphenyl groups. The gerronemins blocked the inducible expression of a hCOX-2 and iNOS promoter driven reporter gene with IC50-values of 1-5 microg/ml. In addition, cytotoxic activities were observed which were due the inhibition of cellular macromolecular syntheses.     

Antiplasmodial activity of naphthoquinones and one anthraquinone from Stereospermum kunthianum

Six new partheniol metabolites were isolated from the biotransformation reaction with Mucor circinelloides ATCC 15242. These metabolites are: humula-1(10), 4, 7-trien-6alpha-ol 2, maali-3-en-8alpha-ol 3, aromadendrane-4alpha, 8alpha, 10alpha-triol 4, maaliane-4alpha, 8alpha, 9alpha-triol 5, maaliane-5alpha, 8alpha, 9alpha-triol 6, 5(9), 6-tricyclohumulane-4alpha, 8alpha, 10alpha-triol 7. The structural assignments of these metabolites were made possible by different spectroscopic means.     

Chemical variability within the marine sponge Aplysina fulva

Dibromotyrosine-derived metabolites are of common occurrence within marine sponges belonging to the order Verongida. However, previous chemical analysis of crude extracts obtained from samples of the verongid sponge Aplysina fulva collected in Brazil did not provide any dibromotyrosine-derived compounds. In this investigation, five samples of A. fulva from five different locations along the Brazilian coastline and one sample from a temperate reef in the South Atlantic Bight (SAB) (Georgia, USA) were investigated for the presence of bromotyrosine-derived compounds. All six samples collected yielded dibromotyrosine-derived compounds, including a new derivative, named aplysinafulvin, which has been identified by analysis of spectroscopic data. These results confirm previous assumptions that dibromotyrosine-derived metabolites can be considered as chemotaxonomic markers of verongid sponges. The isolation of aplysinafulvin provides additional support for a biogenetic pathway involving an arene oxide intermediate in the biosynthesis of Verongida metabolites. It cannot yet be established if the chemical variability observed among the six samples of A. fulva collected in Brazil and the SAB is the result of different environmental factors, distinct chemical extraction and isolation protocols, or a consequence of hidden genetic diversity within the postulated morphological plasticity of this species.     

A prenylated xanthone from Allanblackia floribunda

A new prenylated xanthone, named allanxanthone A, was isolated from the stem bark of Allanblackia floribunda in addition to known compounds, 1,5-dihydoxyxanthone, 1,5,6-trihydroxy-3,7-dimethoxyxanthone, stigmasterol and stigmasteryl-3-O-beta-D-glucopyranoside. The structure of the new compound was assigned as 1,3,5-trihydroxy-2-(3-methylbut-2-enyl)-4-(1,1-dimethylprop-2-enyl) xanthone, by means of spectroscopic analysis. The 13C NMR spectral data of 1,5-dihydroxyxanthone is reported here for the first time as well as the in vitro cytotoxic activity of xanthone metabolites against the KB cell line.     

Anti-protozoal and plasmodial FabI enzyme inhibiting metabolites of Scrophularia lepidota roots

The ethanolic root extract of Scrophularia lepidota, an endemic plant of the Turkish flora, has been investigated for its anti-protozoal and inhibitory effect towards plasmodial enoyl-ACP reductase (FabI), a key enzyme of fatty acid biosynthesis in Plasmodium falciparum. Chromatographic separation of the extract yielded 10 iridoids (1-10), two of which are new, and a known phenylethanoid glycoside (11). The structures of the new compounds were determined as 3,4-dihydro-methylcatalpol (8) and 6-O-[4'-O-trans-(3,4-dimethoxycinnamoyl)-alpha-L-rhamnopyranosyl]aucubin (scrolepidoside, 9) by spectroscopic means. The remaining metabolites were characterized as catalpol (1), 6-O-methylcatalpol (2), aucubin (3), 6-O-alpha-L-rhamnopyranosyl-aucubin (sinuatol, 4), 6-O-beta-D-xylopyranosylaucubin (5), ajugol (6), ajugoside (7), an iridoid-related aglycone (10) and angoroside C (11). Nine isolates were active against Leishmania donovani, with the new compound 9 being most potent (IC50 6.1 microg/ml). Except for 4, all pure compounds revealed some trypanocidal potential against Trypanosoma brucei rhodesiense (IC50 values 29.3-73.0 microg/ml). Only compound 10 showed moderate anti-plasmodial (IC50 40.6 microg/ml) and FabI enzyme inhibitory activity (IC50 100 microg/ml). 10 is the second natural product inhibiting the fatty acid biosynthesis of Plasmodium falciparum.     

Hericenols A-D and a chromanone from submerged cultures of a Stereum species

Extracts of submerged cultures of a Stereum species afforded four new pentasubstituted phenolic compounds, named hericenols A, B, C, and D (1-4), 6-hydroxymethyl-2,2-dimethylchroman-4-one (5) and the known erinapyrone C. Hericenol A (1) showed weak antimicrobial activity while hericenol C (3) was weakly cytotoxic. The structures of the metabolites were determined by spectroscopic techniques.     

Chemistry and weak antimicrobial activities of phomopsins produced by mangrove endophytic fungus Phomopsis sp. ZSU-H76

Three metabolites named phomopsin A (1), B (2) and C (3), together with two known compounds cytosporone B (4) and C (5), were isolated from the mangrove endophytic fungus, Phomopsis sp. ZSU-H76 obtained from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly by 1D and 2D NMR spectroscopic techniques. The medium-sized cyclic phenol ether based on 1 or 2 is rare in natural products. In bioassays, compounds 1, 2, and 3 had no significant antibiotic activities, but compounds 4 and 5 inhibited two fungi Candida albicans and Fusarium oxysporum with an MIC ranging from 32 to 64 microg/ml.     

Sinugrandisterols A-D, trihydroxysteroids from the soft coral Sinularia grandilobata

Four new trihydroxysteroids, sinugrandisterols A-D (1-4), have been isolated from the CH₂Cl₂-soluble fraction of the EtOH extract of Sinularia grandilobata. The structures of these metabolites were determined on the basis of spectroscopic (IR, MS, and 1D and 2D NMR) analysis. The cytotoxicity of 1-4 toward a limited panel of cancer cell lines is also reported.     

(6S)-Hydroxy-3-oxo-alpha-ionol glucosides from Capparis spinosa fruits

Two new (6S)-hydroxy-3-oxo-alpha-ionol glucosides, together with corchoionoside C ((6S,9S)-roseoside) and a prenyl glucoside, were isolated from mature fruits of Capparis spinosa. The structures were established on the basis of spectroscopic, chiroptic and chemical evidence. In addition, the 13C-resonance of C-9 was found to be of particular diagnostic value in assigning the absolute configuration at that center in ionol glycosides. The alpha-ionol derivatives are metabolites of (+)-(S)-abscisic acid.     

New 19-oxygenated and 4-methylated steroids from the Formosan soft coral Nephthea chabroli

Chemical investigation of the Formosan soft coral Nephthea chabroli resulted in the isolation of four new 19-oxygenated steroids, nebrosteroids I-L (1-4), together with a new 4α-methylated steroid, nebrosteroid M (5). The molecular structures of these isolated metabolites were elucidated on the basis of extensive spectroscopic analysis and by comparison of the data with those of related metabolites. Compounds 1-5 were evaluated for anti-inflammatory activity using RAW 264.7 macrophages.     

Xanthohumol metabolites in faeces of rats

Xanthohumol (1), isolated from hop, was fed to rats in a dose of 1000 mg kg(-1) body weight. The faeces of the animals were collected after 24 and 48 h and analysed for metabolites of 1. Approximately 89% of the recovered flavonoid-compounds consisted of unchanged 1. Sixteen metabolites and six previously known metabolites were isolated and characterized by coupling techniques (HPLC-NMR, HPLC-MS and HPLC-DAD). Their structures were elucidated by spectroscopic methods, especially using NMR spectroscopy. Twenty metabolites had a modified chalcone structure and two metabolites were flavanone derivatives.     

Pterocarpans from Bituminaria morisiana and Bituminaria bituminosa

The aerial parts of Mediterranean papilionaceous plants Bituminaria morisiana and B. bituminosa afforded, along with known phenolics, the prenylated pterocarpans bitucarpin A and B, whose structure was elucidated by spectroscopic techniques. A known isoflavonoid (8-prenyldaidzein) was also obtained for the first time as a genuine plant constituent. The accumulation of pterocarpans at the expense of biogenetically more primitive shikimate metabolites like furanocoumarins or isoflavonoids supports the inclusion of this plant, once part of the genus Psoralea, into the distinct genus Bituminaria.     

The metabolites of the mangrove fungus Verruculina enalia No. 2606 from a salt lake in the Bahamas

Two metabolites enalin A (1) and B (2), together with hydroxymethyl furfural (3) and three cyclodipeptides (4, 5 and 6), were isolated from the mangrove fungus Verruculina enaria from a salt lake in the Bahamas. Their structures were determined by spectroscopic methods, mainly by 2D NMR spectroscopic analyses. A possible biosynthetic scheme to 1 and 2 is presented.     

Three isocoumarins and a benzofuran from the cultured lichen mycobionts of Pyrenula sp

The spore-derived mycobionts of the lichen Pyrenula sp. were cultivated on a malt-yeast extract medium supplemented with 10% sucrose. The investigation of their metabolites resulted in isolation of four compounds, three isocoumarins and a biogenetically related benzofuran; their structures were determined by spectroscopic methods.     

Penicidones A-C, three cytotoxic alkaloidal metabolites of an endophytic Penicillium sp

Along with the known secondary metabolites lumichrome, physcion, and emodin-1,6-dimethyl ether, three alkaloids named penicidones A-C (1-3) were isolated from the culture of Penicillium sp. IFB-E022, an endophytic fungal strain residing in the stem of Quercus variabilis (Fagaceae). The structures of penicidones A-C were established by a correlative interpretation of spectroscopic data including IR, UV and HR-ESI-MS, as well as by analysis of a set of 1D and 2D NMR experiments. The stereochemistry of compounds 1 and 2 was obtained by comparison of the optical rotation with those of vermistatin and its analogues. Penicidones A-C were the first group of natural products possessing a penicidone framework. Compounds 1-3 exhibited moderate cytotoxicity against four cancer cell lines.     

Antimicrobial metabolites produced by an intertidal Acremonium furcatum

In a screening for antimicrobial metabolites, amides of D-allo- and L-isoleucine derivatives were isolated from the culture of a marine strain of Acremonium furcatum. Structural elucidation of these compounds was performed by analysis of spectroscopic data and confirmed by synthesis. All of the compounds, natural and synthetic intermediates, were bioassayed against bacteria and phytopathogenic fungi, with many showing remarkable antifungal activities.     

Ophiobolin E and 8-epi-ophiobolin J produced by Drechslera gigantea, a potential mycoherbicide of weedy grasses

Drechslera gigantea, a fungal pathogen isolated from large crabgrass (Digitaria sanguinalis) and proposed as a potential mycoherbicide of grass weeds, produces phytotoxic metabolites in liquid and solid cultures. Ophiobolin A and three minor ophiobolins i.e., 6-epi-ophiobolin A, 3-anhydro-6-epi-ophiobolin A and ophiobolin I were obtained from the liquid culture broths. Interestingly and unexpectedly, ophiobolins also appeared in cultures of this fungus and they were isolated together with the known ophiobolins B and J, and designed as ophiobolin E and 8-epi-ophiobolin J. They were characterized using essentially spectroscopic methods. It is noteworthy that D. gigantea produces such a plethora of bioactive organic substances. Some structure-activity relationship results are also discussed in this report.     

Eudesmane and megastigmane glucosides from Laggera alata

Four eudesmane glucosides, alatosides A-D (1-4), and one megastigmane glucoside, alatoside E (5), were isolated from the BuOH fraction of Laggera alata along with six known compounds. Structures of the new compounds were elucidated by a combination of chemical and spectroscopic methods. Alatosides A-E were characterized as: 1alpha-O-(beta-D-glucopyranosyloxyl)-7-epi-eudesma-11-en-2beta,4alpha-diol (1), 2beta-O-(beta-D-glucopyranosyloxyl)-eudesma-4alpha-hydroxyl-11(13)-en-12-oic-acid (2), 5beta-O-(beta-D-glucopyranosyloxyl)-eudesma-4(15),11(13)-dien-12-oic-acid (3), 5alpha-O-(beta-D-glucopyranosyloxyl)-eudesma-3,11(13)-dien-12-oic acid (4) and 3beta-O-(beta-D-glucopyranosyloxyl)-megastigma-9-one (5), respectively. Based on the chemical characteristics of eudesmane derivatives isolated from the Laggera genus, it was suggested that there are probably two different biogenetic pathways for these secondary metabolites in this genus.     

3-Methylbutanoyl and 3-methylbut-2-enoyl disaccharides from green coffee beans (Coffea arabica)

The aerial parts of Teucrium oliverianum yielded two neo-clerodane diterpenoids, teucrolin F and G, together with the known teucrolin E. The previously proposed structure for teucrolin E was revised so that it contains a tetrahydrofuran ring instead of an oxetane ring. This was based on analysis of the NMR spectroscopic data of its diacetate, including its NOE spectra. In addition, the structural assignments of the new diterpenoids were based on 1H and 13C NMR spectroscopic studies, mainly 2D NMR experiments, including homonuclear and heteronuclear correlations.