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. (C) 2007 Elsevier Ltd. All rights reserved.

Antiparasitic, antineuroinflammatory, and cytotoxic polyketides from the marine sponge Plakortis angulospiculatus collected in Brazil

Investigation of the bioactive crude extract from the sponge Plakortis angulospiculatus from Brazil led to the isolation of plakortenone (1) as a new polyketide, along with five known polyketides (2-6) previously isolated from other Plakortis sponges. The known polyketides were tested in antileishmanial, antitrypanosomal, antineuroinflammatory, and cytotoxicity assays. The results show that plakortide P (3) is a potent antiparasitic compound, against both Leishmania chagasi and Trypanosona cruzi, and exhibited antineuroinflammatory activity. The known polyketides 2-6 were tested for cytotoxicity against four human cancer cell lines, but displayed only moderate cytotoxic activity.

Pyrodysinoic Acid Derivatives from the Marine Sponge Dysidea robusta

Three new nitrogen-containing terpenes related to pyrodysinoic acid (1) have been isolated from the sponge Dysidea robusta collected in Brazil. Isopyrodysinoic acid (2), 13-hydroxyisopyrodysinoic acid (3), and pyrodysinoic acid B (4) were obtained from the crude extract of D. robusta and identified by analysis of spectroscopic data. Pyrodysinoic acid B (4) is the first furodysin or furodysinin sesquiterpene derivative with a trans junction between the two six-membered rings of the 1,2,3,4,4a,7,8,8a-octahydro-1,1,6-trimethylnaphthalene moiety.

Candida species: Current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, which retain many side effects. Candida species are major human fungal pathogens that cause both mucosal and deep tissue infections. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth. Biofilms are biological communities with a high degree of organization, in which micro-organisms form structured, coordinated and functional communities. These biological communities are embedded in a self-created extracellular matrix. Biofilm production is also associated with a high level of antimicrobial resistance of the associated organisms. The ability of Candida species to form drugresistant biofilms is an important factor in their contribution to human disease. The study of plants as an alternative to other forms of drug discovery has attracted great attention because, according to the World Health Organization, these would be the best sources for obtaining a wide variety of drugs and could benefit a large population. Furthermore, silver nanoparticles, antibodies and photodynamic inactivation have also been used with good results. This article presents a brief review of the literature regarding the epidemiology of Candida species, as well as their pathogenicity and ability to form biofilms, the antifungal activity of natural products and other therapeutic options. © 2013 SGM.

Two Polyketides from a Co-culture of Two Marine-derived Fungal Strains

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

New drugs with antiprotozoal activity from marine algae: a review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Carmaphycins: New Proteasome Inhibitors Exhibiting an alpha,beta-Epoxyketone Warhead from a Marine Cyanobacterium

Two new peptidic proteasome inhibitors were isolated as trace components from a Curacao collection of the marine cyanobacterium Symploca sp. Carmaphycin A (1) and carmaphycin B (2) feature a leucine-derived a,beta-epoxyketone warhead directly connected to either methionine sulfoxide or methionine sulfone. Their structures were elucidated on the basis of extensive NMR and MS analyses and confirmed by total synthesis, which in turn provided more material for further biological evaluations. Pure carmaphycins A and B were found to inhibit the beta 5 subunit (chymotrypsin-like activity) of the S. cerevisiae 20S proteasome in the low nanomolar range. Additionally, they exhibited strong cytotoxicity to lung and colon cancer cell lines, as well as exquisite antiproliferative effects in the NCI60 cell-line panel. These assay results as well as initial structural biology studies suggest a distinctive binding mode for these new inhibitors.

11-Oxoaerothionin isolated from the marine sponge Aplysina fistularis shows anti-inflammatory activity in LPS-stimulated macrophages

Marine sponges of the order Verongida are a rich source of biologically active bromotyrosine-derived secondary metabolites. However, none of these compounds are known to display anti-inflammatory activity. In the present investigation, we report the anti-inflammatory effects of 11-oxoaerothionin isolated from the Verongida sponge Aplysina fistularis. When RAW264.7 cells and primary macrophages were preincubated with 11-oxoaerothionin and stimulated with LPS (lipopolysaccharide), a concentration-dependent inhibition of iNOS (inducible nitric oxide synthase) protein and NO2- (Nitrite) production were observed. The same effect was observed when proinflammatory cytokines and PGE(2) (Prostaglandin E2) production was evaluated. In summary, we demonstrated that in the presence of LPS, 11-oxoaerothionin suppresses NO2 and iNOS expression as well as inflammatory cytokines and PGE(2).

Molluscicidal activity of some marine substances against the snail Biomphalaria glabrata (Mollusca, Planorbidae)

Freshwater snails of the genus Biomphalaria play a major role as intermediate hosts of Schistosoma mansoni, the etiologic agent of schistosomiasis. While Biomphalaria spp. control by molluscicides is one of the main strategies to reduce the snail population in infected areas, there are few effective molluscicides commercially available. Natural products may be considered as potentially useful and safe molluscicides. We have evaluated the molluscicidal activity of 12 extracts from ten marine organisms on adult and embryonic stages of Biomphalaria glabrata. Only extracts of the red algae Liagora farinosa and of the sponge Amphimedon viridis presented molluscicidal activity. Lethal concentration (LC)(50) values obtained were 120 mu g/mL for L. farinosa CH2Cl2 extract (apolar fraction) and 20 mu g/mL for A. viridis extract and halitoxin. The polar alga fraction and halitoxin had no effect on B. glabrata embryos. The algae apolar fraction was active on B. glabrata in all embryonic development stages, with LC50 values for blastulae at 42 mu g/mL, gastrulae at 124 mu g/mL, trochophore at 180 mu g/mL, and veliger at 222 mu g/mL. This is the first report of extracts from marine organisms which presented molluscicidal activity.

Systematic UPLC-ESI-MS/MS Study on the Occurrence of Staurosporine and Derivatives in Associated Marine Microorganisms from Eudistoma vannamei

Former bioactivity-guided analysis of the marine invertebrate Eudistoma vannamei led to the isolation of staurosporine derivatives, which revealed strong cytotoxic activity against several human cancer cell lines. The occurrence of such alkaloids in E. vannamei may be correlated to the presence of associated biota, such as Streptomyces bacteria. In agreement to this hypothesis, marine microorganisms associated with E. vannamei were recovered and cultured, leading to a total of 84 isolated bacterial strains. Gas phase fragmentation reactions of staurosporine and derivatives were systematically studied and the analyzed results further supported by computational chemistry studies. The resulting fragment patterns were used to search for the presence of different derivatives in extracts of isolated microorganisms, thereby using LC-MS/MS analysis in MRM mode. These results evidenced that one isolated Streptomyces sp. was able to generate staurosporine, while none of the hydroxy-7-oxo derivatives were detected. Finally, significant cytotoxic activity against human cancer lines was observed for one of the extracts.

Nematocidal thiocyanatins from a southern Australian marine sponge Oceanapia sp.

Investigations of a southern Australian marine sponge, Oceanapia sp., have yielded two new methyl branched bisthiocyanates, thiocyanatins D-1 (3a) and D-2 (3b), along with two new thiocarbamate thiocyanates, thiocyanatins E-l (4a) and E-2 (4b). The new thiocyanatins belong to a rare class of bioactive marine metabolite previously only represented by thiocyanatins A-C (1, 2a/b). Structures were assigned on the basis of detailed spectroscopic analysis, with comparisons to the known bisthiocyanate thiocyanatin A (1) and synthetic model compounds (5-7). The thiocyanatins exhibit potent nematocidal activity, and preliminary structure-activity relationship investigations have confirmed key characteristics of the thiocyanatin pharmacophore.

Tetra- and tribromopbenoxyanisoles in Marine Samples from Oceania

Some methoxylated polybrominated diphenyl ethers (MeO-BDEs) are known halogenated natural products (HNPs) and are frequently detected in higher organisms of the marine environment. In this study we demonstrate that a prominent MeO-BDE, previously detected in marine mammals from Australia, is identical to 3,5-dibromo-2-(2',4'-dibromo)phenoxyanisole(BC-3,6-MeO-BDE47). Up to 1.9mg/ kg of 6-MeO-BDE 47 was present in cetaceans from Australia, 0.2-0.3 mg/kg in two crocodile eggs from Australia, but concentrations of 1 or 2 orders of magnitude lower were found in shark liver oil from New Zealand and in marine mammals from Africa and the Antarctic. Concentrations of 6-MeO-BDE47 in samples from Australia were in the same range as anthropogenic pollutants such as PCB 153 and p,p'-DDE. Along with 6-MeO-BDE 47 and the known HNP 4,6-dibromo-2-(2',4'-dibromo)phenoxyanisole (BC-2,2'-MeO-BDE 68), several tribromophenoxyanisoles (MeO-triBDE) were present in tissue of Australian cetaceans. To determine their structure, abiotic debromination experiments were performed using 6-MeO-BDE 47 and 2'-MeO-BDE 68 and superreduced di cyanocobalamine. These experiments resulted in formation of eight MeO-triBDEs, all of which were detected in the cetacean samples. Five of these eight MeO-triBDEs could be identified based on two standard compounds as well as gas chromatographic and mass spectrometric features. It was also shown that the first eluting isomer (compound 1), 6-MeO-BDE 17 (compound 2), and 2-MeO-BDE 39 (compound 5) were the most prominent MeO-triBDEs in the Australian cetacean samples. The concentrations of the MeO-triBDEs in two cetacean samples were 0.20 and 0.36 mg/kg, respectively. Although the reductive debromination with dicyanocobalamine resulted in a different congener pattern than was found in the marine mammals, it could not be excluded that the tribromo congeners of 6-MeO-BDE 47 and 2'-MeO-BDE 68 in the samples were metabolites of the latter.

Spongosoritin A: A new polyketide from a Fijian marine sponge, Spongosorites sp.

A new polyketide, spongosoritin A, with a rare vinylagous alpha,beta-unsaturated gamma-lactone moiety was isolated from a Fijian marine sponge, Spongosorites sp., and the structure assigned by detailed spectroscopic analysis.

N-3,5 '-cycloxanthosine, the first natural occurrence of a cyclonucleoside

An Eryus sp. of marine sponge from the Great Australian Bight has yielded the first reported natural occurrence of a cyclonucleoside, N-3,5'-cycloxanthosine. The structure of N-3,5'-cycloxanthosine was confirmed by detailed spectroscopic analysis and total synthesis.