Antiprotozoal activities of organic extracts from French marine seaweeds

Marine macrophytes contain a variety of biologically active compounds, some reported to have antiprotozoal activity in vitro. As a part of a screening program to search for new natural antiprotozoals, we screened hydroalcoholic and ethyl acetate extracts of 20 species of seaweeds from three phyla (Rhodophyta, Heterokontophyta and Chlorophyta), sampled along the Normandy (France) coast. We tested them in vitro against the protozoa responsible for three major endemic parasitic diseases: Plasmodium falciparum, Leishmania donovani and Trypanosoma cruzi. The selectivity of the extracts was also evaluated by testing on a mammalian cell line (L6 cells). Ethyl acetate extracts were more active than hydroalcoholic ones. Activity against T. cruzi and L. donovani was non-existent to average, but almost half the extracts showed good activity against P. falciparum. The ethyl acetate extract of Mastocarpus stellatus showed the best antiplasmodial activity as well as the best selectivity index (IC(50) = 2.8 μg/mL; SI > 30). Interestingly, a red algae species, which shares phylogenetic origins with P. falciparum, showed the best antiplasmodial activity. This study is the first to report comparative antiprotozoal activity of French marine algae. Some of the species studied here have not previously been biologically evaluated.     

Assessment of the Antimicrobial Activity of Algae Extracts on Bacteria Responsible of External Otitis

External otitis is a diffuse inflammation around the external auditory canal and auricle, which is often occurred by microbial infection. This disease is generally treated using antibiotics, but the frequent occurrence of antibiotic resistance requires the development of new antibiotic agents. In this context, unexplored bioactive natural candidates could be a chance for the production of targeted drugs provided with antimicrobial activity. In this paper, microbial pathogens were isolated from patients with external otitis using ear swabs for over one year, and the antimicrobial activity of the two methanol extracts from selected marine (Dunaliella salina) and freshwater (Pseudokirchneriella subcapitata) microalgae was tested on the isolated pathogens. Totally, 114 bacterial and 11 fungal strains were isolated, of which Staphylococcus spp. (28.8%) and Pseudomonas aeruginosa (P. aeruginosa) (24.8%) were the major pathogens. Only three Staphylococcus aureus (S. aureus) strains and 11 coagulase-negative Staphylococci showed resistance to methicillin. The two algal extracts showed interesting antimicrobial properties, which mostly inhibited the growth of isolated S. aureus, P. aeruginosa, Escherichia coli, and Klebsiella spp. with MICs range of 1.4 × 10⁹ to 2.2 × 10¹⁰ cells/mL. These results suggest that the two algae have potential as resources for the development of antimicrobial agents.     

New cytotoxic oxygenated sterols from the marine bryozoan Cryptosula pallasiana

Six new sterols (1-6), together with seven known sterols (7-13), were isolated from the CCl(4) extract of the marine bryozoan Cryptosula pallasiana, four (3-6) of which have already been reported as synthetic sterols. This is the first time that these compounds (3-6) are reported as natural sterols. The structures of the new compounds were determined on the basis of the extensive spectroscopic analysis, including two-dimensional (2D) NMR and HR-ESI-MS data. Compounds 1-4, 7 and 10-13 were evaluated for their cytotoxicity against HL-60 human myeloid leukemia cell line, and all of the evaluated compounds exhibited moderate cytotoxicity to HL-60 cells with a range of IC(50) values from 14.73 to 22.11 μg/mL except for compounds 12 and 13.     

Antibacterial compounds from marine Vibrionaceae isolated on a global expedition

On a global research expedition, over 500 bacterial strains inhibitory towards pathogenic bacteria were isolated. Three hundred of the antibacterial strains were assigned to the Vibrionaceae family. The purpose of the present study was to investigate the phylogeny and bioactivity of five Vibrionaceae strains with pronounced antibacterial activity. These were identified as Vibrio coralliilyticus (two strains), V. neptunius (two strains), and Photobacterium halotolerans (one strain) on the basis of housekeeping gene sequences. The two related V. coralliilyticus and V. neptunius strains were isolated from distant oceanic regions. Chemotyping by LC-UV/MS underlined genetic relationships by showing highly similar metabolite profiles for each of the two V. coralliilyticus and V. neptunius strains, respectively, but a unique profile for P. halotolerans. Bioassay-guided fractionation identified two known antibiotics as being responsible for the antibacterial activity; andrimid (from V. coralliilyticus) and holomycin (from P. halotolerans). Despite the isolation of already known antibiotics, our findings show that marine Vibrionaceae are a resource of antibacterial compounds and may have potential for future natural product discovery.     

Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium

During a global research expedition, more than five hundred marine bacterial strains capable of inhibiting the growth of pathogenic bacteria were collected. The purpose of the present study was to determine if these marine bacteria are also a source of compounds that interfere with the agr quorum sensing system that controls virulence gene expression in Staphylococcus aureus. Using a gene reporter fusion bioassay, we recorded agr interference as enhanced expression of spa, encoding Protein A, concomitantly with reduced expression of hla, encoding α-hemolysin, and rnaIII encoding RNAIII, the effector molecule of agr. A marine Photobacterium produced compounds interfering with agr in S. aureus strain 8325-4, and bioassay-guided fractionation of crude extracts led to the isolation of two novel cyclodepsipeptides, designated solonamide A and B. Northern blot analysis confirmed the agr interfering activity of pure solonamides in both S. aureus strain 8325-4 and the highly virulent, community-acquired strain USA300 (CA-MRSA). To our knowledge, this is the first report of inhibitors of the agr system by a marine bacterium.     

Deoxyuridines from the marine sponge associated actinomycete Streptomyces microflavus

One new nucleoside derivative, named 3-acetyl-5-methyl-2'-deoxyuridine (1), along with two known compounds 3,5-dimethyl-2'-deoxyuridine (2) and 3-methyl-2'-deoxyuridine (3), were isolated from the cultures of Streptomyces microflavus. This strain was an associated actinomycete isolated from the marine sponge Hymeniacidon perlevis collected from the coast of Dalian (China). Their structures were elucidated by detailed NMR and MS spectroscopic analysis as well as comparison with literature data.     

A new anthracene derivative from marine Streptomyces sp. W007 exhibiting highly and selectively cytotoxic activities

A new anthracene derivative, 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3, 4-tetrahydro-benz[α]anthracene, was isolated from the marine strain Streptomyces sp. W007, and its structure was established by spectroscopic analysis including mass spectra, 1D- and 2D-NMR ((1)H-(1)H COSY, HMBC, HSQC and NOESY) experiments. 3-hydroxy-1-keto-3-methyl-8-methoxy-1,2,3,4-tetrahydro-benz[α]anthracene showed cytotoxicity against human lung adenocarcinoma cell line A549.     

Kiamycin, a unique cytotoxic angucyclinone derivative from a marine Streptomyces sp

Kiamycin (1), a new angucyclinone derivative possessing an 1,12-epoxybenz[a]anthracene ring system, was isolated from the marine Streptomyces sp. strain M268 along with the known compounds 8-O-methyltetrangomycin (3) and 8-O-methylrabelomycin (4). Their structures were elucidated by detailed spectroscopic analysis and comparison with literature data. The new angucyclinone derivative showed inhibitory activities against the human cell lines HL-60 (leukemia), A549 (lung adenocarcinoma), and BEL-7402 (hepatoma) with inhibition rates of 68.2%, 55.9%, and 31.7%, respectively, at 100 μM. It appears to have potential as an anticancer agent with selective activity.     

Toward the synthesis and biological screening of a cyclotetrapeptide from marine bacteria

The first synthesis of a naturally occurring tetrapeptide cyclo-(isoleucyl-prolyl-leucyl-alanyl) has been achieved using a solution-phase technique via coupling of dipeptide segments Boc-L-Pro-L-Leu-OH and L-Ala-L-Ile-OMe. Deprotection of the linear tetrapeptide unit and its subsequent cyclization gave a cyclopeptide, identical in all aspects to the naturally occurring compound. Bioactivity results indicated the antifungal and antihelmintic potential of the synthesized peptide against pathogenic dermatophytes and earthworms.     

Yessotoxins, a group of marine polyether toxins: an overview

Yessotoxin (YTX) is a marine polyether toxin that was first isolated in 1986 from the scallop Patinopecten yessoensis. Subsequently, it was reported that YTX is produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. YTXs have been associated with diarrhetic shellfish poisoning (DSP) because they are often simultaneously extracted with DSP toxins, and give positive results when tested in the conventional mouse bioassay for DSP toxins. However, recent evidence suggests that YTXs should be excluded from the DSP toxins group, because unlike okadaic acid (OA) and dinophyisistoxin-1 (DTX-1), YTXs do not cause either diarrhea or inhibition of protein phosphatases. In spite of the increasing number of molecular studies focused on the toxicity of YTX, the precise mechanism of action is currently unknown. Since the discovery of YTX, almost forty new analogues isolated from both mussels and dinoflagellates have been characterized by NMR or LC-MS/MS techniques. These studies indicate a wide variability in the profile and the relative abundance of YTXs in both, bivalves and dinoflagellates. This review covers current knowledge on the origin, producer organisms and vectors, chemical structures, metabolism, biosynthetic origin, toxicological properties, potential risks to human health and advances in detection methods of YTXs.     

Chemical Composition and Antioxidant/Antimicrobial Activities in Supercritical Carbon Dioxide Fluid Extract of Gloiopeltis tenax

Gloiopeltis tenax (G. tenax) is widely distributed along the Chinese coastal areas and is commonly used in the treatment of diarrhea and colitis. This study aimed at investigating the bioactivities of the volatile constituents in G. tenax. We extracted the essential constituents of G. tenax by supercritical carbon dioxide extraction (CO₂-SFE), then identified and analyzed the constituents by gas chromatography-mass spectrometry (GC-MS). In total, 30 components were identified in the G. tenax extract. The components showed remarkable antioxidant activity (radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH)), lipid peroxidation inhibition capacity (in a β-carotene/linoleic acid-coupled oxidation reaction), and hydroxyl radical-scavenging activity (by deoxyribose degradation by iron-dependent hydroxyl radical), compared to butylated hydroxytoluene. In microdilution assays, G. tenax extracts showed a moderate inhibitory effects on Staphyloccocus aureus (minimum inhibitory concentration (MIC) = 3.9 mg/mL), Enterococcus faecalis (7.8 mg/mL), Pseudomonas aeruginosa (15.6 mg/mL), and Escherichia coli (3.9 mg/mL). Antioxidant and antimicrobial activities of G. tenax were related to the active chemical composition. These results suggest that the CO₂-SFE extract from G. tenax has potential to be used as a natural antioxidant and antimicrobial agent in food processing.     

Bioactive indole derivatives from the South Pacific marine sponges Rhopaloeides odorabile and Hyrtios sp

Indole derivatives including bromoindoles have been isolated from the South Pacific marine sponges Rhopaloeides odorabile and Hyrtios sp. Their structures were established through analysis of mass spectra and 1D and 2D NMR spectroscopic data. Their potential inhibitory phospholipase A₂ (PLA₂), antioxidant and cytotoxic activities were evaluated. The new derivative 5,6-dibromo-l-hypaphorine (9) isolated from Hyrtios sp. revealed a weak bee venom PLA₂ inhibition (IC₅₀ 0.2 mM) and a significant antioxidant activity with an Oxygen Radical Absorbance Capacity (ORAC) value of 0.22. The sesquiterpene aureol (4), also isolated from Hyrtios sp., showed the most potent antioxidant activity with an ORAC value of 0.29.     

Hepatotoxic Seafood Poisoning (HSP) Due to Microcystins: A Threat from the Ocean?

Cyanobacterial blooms are a major and growing problem for freshwater ecosystems worldwide that increasingly concerns public health, with an average of 60% of blooms known to be toxic. The most studied cyanobacterial toxins belong to a family of cyclic heptapeptide hepatotoxins, called microcystins. The microcystins are stable hydrophilic cyclic heptapeptides with a potential to cause cell damage following cellular uptake via organic anion-transporting proteins (OATP). Their intracellular biologic effects presumably involve inhibition of catalytic subunits of protein phosphatases (PP1 and PP2A) and glutathione depletion. The microcystins produced by cyanobacteria pose a serious problem to human health, if they contaminate drinking water or food. These toxins are collectively responsible for human fatalities, as well as continued and widespread poisoning of wild and domestic animals. Although intoxications of aquatic organisms by microcystins have been widely documented for freshwater ecosystems, such poisonings in marine environments have only occasionally been reported. Moreover, these poisonings have been attributed to freshwater cyanobacterial species invading seas of lower salinity (e.g., the Baltic) or to the discharge of freshwater microcystins into the ocean. However, recent data suggest that microcystins are also being produced in the oceans by a number of cosmopolitan marine species, so that Hepatotoxic Seafood Poisoning (HSP) is increasingly recognized as a major health risk that follows consumption of contaminated seafood.     

Brominated compounds from marine sponges of the genus Aplysina and a compilation of their 13C NMR spectral data

Aplysina is the best representative genus of the family Aplysinidae. Halogenated substances are its main class of metabolites. These substances contribute greatly to the chemotaxonomy and characterization of the sponges belonging to this genus. Due to their pharmacological activities, these alkaloids are of special interest. The chemistry of halogenated substances and of the alkaloids has long been extensively studied in terrestrial organisms, while the number of marine organisms studied has just started to increase in the last decades. This review describes 101 halogenated substances from 14 species of Aplysina from different parts of the world. These substances can be divided into the following classes: bromotyramines (A), cavernicolins (B), hydroverongiaquinols (C), bromotyrosineketals (D), bromotyrosine lactone derivatives (E), oxazolidones (F), spiroisoxazolines (G), verongiabenzenoids (H), verongiaquinols (I), and dibromocyclohexadienes (J). A compilation of their (13)C NMR data is also part of the review. For this purpose 138 references were consulted.     

Phenolic Polyketides from the Co-Cultivation of Marine-Derived Penicillium sp. WC-29-5 and Streptomyces fradiae 007

Penicillium sp. WC-29-5 was co-cultured with Streptomyces fradiae 007 to produce five natural products (1–3, 4a and 4b) that were isolated and characterized by spectroscopic analysis. Interestingly, these compounds were found to be different from those produced in discrete fungal and bacterial controls. Among these compounds, the absolute configurations of compounds 4a and 4b were determined for the first time by X-ray single crystal diffraction experiments and electronic circular dichroism (ECD) calculations. An evaluation of the cytotoxic activities of these compounds revealed that 4b was moderately cytotoxic towards HL-60 and H1975 tumor cells with IC₅₀ values of 3.73 and 5.73 µM, respectively, whereas compound 4a was only moderately cytotoxic towards H1975 cells with an IC₅₀ value of 3.97 µM.     

Antimicrobial Action of Compounds from Marine Seaweed

Seaweed produces metabolites aiding in the protection against different environmental stresses. These compounds show antiviral, antiprotozoal, antifungal, and antibacterial properties. Macroalgae can be cultured in high volumes and would represent an attractive source of potential compounds useful for unconventional drugs able to control new diseases or multiresistant strains of pathogenic microorganisms. The substances isolated from green, brown and red algae showing potent antimicrobial activity belong to polysaccharides, fatty acids, phlorotannins, pigments, lectins, alkaloids, terpenoids and halogenated compounds. This review presents the major compounds found in macroalga showing antimicrobial activities and their most promising applications.     

Phylogeny of Penicillium and the segregation of Trichocomaceae into three families

Species of Trichocomaceae occur commonly and are important to both industry and medicine. They are associated with food spoilage and mycotoxin production and can occur in the indoor environment, causing health hazards by the formation of β-glucans, mycotoxins and surface proteins. Some species are opportunistic pathogens, while others are exploited in biotechnology for the production of enzymes, antibiotics and other products. Penicillium belongs phylogenetically to Trichocomaceae and more than 250 species are currently accepted in this genus. In this study, we investigated the relationship of Penicillium to other genera of Trichocomaceae and studied in detail the phylogeny of the genus itself. In order to study these relationships, partial RPB1, RPB2 (RNA polymerase II genes), Tsr1 (putative ribosome biogenesis protein) and Cct8 (putative chaperonin complex component TCP-1) gene sequences were obtained. The Trichocomaceae are divided in three separate families: Aspergillaceae, Thermoascaceae and Trichocomaceae. The Aspergillaceae are characterised by the formation flask-shaped or cylindrical phialides, asci produced inside cleistothecia or surrounded by Hülle cells and mainly ascospores with a furrow or slit, while the Trichocomaceae are defined by the formation of lanceolate phialides, asci borne within a tuft or layer of loose hyphae and ascospores lacking a slit. Thermoascus and Paecilomyces, both members of Thermoascaceae, also form ascospores lacking a furrow or slit, but are differentiated from Trichocomaceae by the production of asci from croziers and their thermotolerant or thermophilic nature. Phylogenetic analysis shows that Penicillium is polyphyletic. The genus is re-defined and a monophyletic genus for both anamorphs and teleomorphs is created (Penicillium sensu stricto). The genera Thysanophora, Eupenicillium, Chromocleista, Hemicarpenteles and Torulomyces belong in Penicilliums. str. and new combinations for the species belonging to these genera are proposed. Analysis of Penicillium below genus rank revealed the presence of 25 clades. A new classification system including both anamorph and teleomorph species is proposed and these 25 clades are treated here as sections. An overview of species belonging to each section is presented. TAXONOMIC NOVELTIES: New sections, all in Penicillium: sect. Sclerotiora Houbraken & Samson, sect. Charlesia Houbraken & Samson, sect. Thysanophora Houbraken & Samson,sect. Ochrosalmonea Houbraken & Samson, sect. Cinnamopurpurea Houbraken & Samson, Fracta Houbraken & Samson, sect. Stolkia Houbraken & Samson, sect. Gracilenta Houbraken & Samson, sect. Citrina Houbraken & Samson, sect. Turbata Houbraken & Samson, sect. Paradoxa Houbraken & Samson, sect. Canescentia Houbraken & Samson. New combinations:Penicillium asymmetricum (Subramanian & Sudha) Houbraken & Samson, P. bovifimosum (Tuthill & Frisvad) Houbraken & Samson, P. glaucoalbidum (Desmazières) Houbraken & Samson, P. laeve (K. Ando & Manoch) Houbraken & Samson, P. longisporum (Kendrick) Houbraken & Samson, P. malachiteum (Yaguchi & Udagawa) Houbraken & Samson, P. ovatum (K. Ando & Nawawi) Houbraken & Samson, P. parviverrucosum (K. Ando & Pitt) Houbraken & Samson, P. saturniforme (Wang & Zhuang) Houbraken & Samson, P. taiwanense (Matsushima) Houbraken & Samson. New names:Penicillium coniferophilum Houbraken & Samson, P. hennebertii Houbraken & Samson, P. melanostipe Houbraken & Samson, P. porphyreum Houbraken & Samson.     

Briarane Diterpenoids Isolated from Gorgonian Corals between 2011 and 2013

The structures, names, bioactivities and references of 138 briarane-type diterpenoids, including 87 new compounds, are summarized in this review. All the briarane-type compounds mentioned in this review article were obtained from gorgonian corals including the genus Briareum, Dichotella, Junceella and Verrucella. Some of these compounds showed potential bioactivities.     

Bioactivity of benthic and picoplanktonic estuarine cyanobacteria on growth of photoautotrophs: inhibition versus stimulation

Understanding potential biochemical interactions and effects among cyanobacteria and other organisms is one of the main keys to a better knowledge of microbial population structuring and dynamics. In this study, the effects of cyanobacteria from benthos and plankton of estuaries on other cyanobacteria and green algae growth were evaluated. To understand how the estuarine cyanobacteria might influence the dynamics of phytoplankton, experiments were carried out with the freshwater species Microcystis aeruginosa and Chlorella sp., and the marine Synechocystis salina and Nannochloropsis sp. exposed to aqueous and organic (70% methanol) crude extracts of cyanobacteria for 96 h. The most pronounced effect observed was the growth stimulation. Growth inhibition was also observed for S. salina and M. aeruginosa target-species at the highest and lowest concentrations of cyanobacterial extracts. The methanolic crude extract of Phormidium cf. chalybeum LEGE06078 was effective against S. salina growth in a concentration-dependent manner after 96 h-exposure. All of the cyanobacterial isolates showed some bioactivity on the target-species growth, i.e., inhibitory or stimulating effects. These results indicate that the analyzed cyanobacterial isolates can potentially contribute to blooms' proliferation of other cyanobacteria and to the abnormal growth of green algae disturbing the dynamic of estuarine phytoplankton communities. Since estuaries are transitional ecosystems, the benthic and picoplanktonic estuarine cyanobacteria can change both freshwater and marine phytoplankton succession, competition and bloom formation. Furthermore, a potential biotechnological application of these isolates as a tool to control cyanobacteria and microalgae proliferation can be feasible. This work is the first on the subject of growth responses of photoautotrophs to cyanobacteria from Atlantic estuarine environments.     

Natural Product Chemistry of Gorgonian Corals of the Family Plexauridae Distributed in the Indo-Pacific Ocean

The structures, names, bioactivities and references of 105 natural products obtained from gorgonian corals belonging to the family Plexauridae with an Indo-Pacific distribution are described in this review. All compounds mentioned in this review were obtained from gorgonian corals belonging to the genera Astrogorgia, Bebryce, Echinomuricea, Euplexaura and Menella.