ABSTRACT
Marine sponges represent a good source of natural metabolites for biotechnological applications in the pharmacological, cosmeceutical, and nutraceutical fields. In the present work, we analyzed the biotechnological potential of the alien species Haliclona (Halichoclona) vansoesti de Weerdt, de Kluijver & Gomez, 1999, previously collected in the Mediterranean Sea (Faro Lake, Sicily). The bioactivity and chemical content of this species has never been investigated, and information in the literature on its Caribbean counterpart is scarce. We show that an enriched extract of H. vansoesti induced cell death in human melanoma cells with an IC50 value of 36.36 µg mL-1, by (i) triggering a pro-inflammatory response, (ii) activating extrinsic apoptosis mediated by tumor necrosis factor receptors triggering the mitochondrial apoptosis via the involvement of Bcl-2 proteins and caspase 9, and (iii) inducing a significant reduction in several proteins promoting human angiogenesis. Through orthogonal SPE fractionations, we identified two active sphingoid-based lipid classes, also characterized by nuclear magnetic resonance and mass spectrometry, as the main components of two active fractions. Overall, our findings provide the first evaluation of the anti-cancer potential of polar lipids isolated from the marine sponge H. (Halichoclona) vansoesti, which may lead to new lead compounds with biotechnological applications in the pharmaceutical field.
Subject(s)
Antineoplastic Agents , Apoptosis , Haliclona , Lipids , Melanoma , Animals , Haliclona/chemistry , Humans , Melanoma/pathology , Melanoma/drug therapy , Melanoma/metabolism , Cell Line, Tumor , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Porifera/chemistryABSTRACT
A lectin from the marine sponge Haliclona (Reniera) implexiformis (HiL) was isolated by affinity chromatography on Sepharose™ matrix. HiL showed specificity for galactose and its derivatives. The glycoproteins porcine stomach mucin (PSM) and bovine stomach mucin (BSM) were potent inhibitors. Hemagglutinating activity of the lectin was maximal between pH 5.0 and 9.0. The lectin remained active until 60°C. The presence of CaCl2 and EDTA did not affect the hemagglutinating activity. In SDS-PAGE, HiL showed a single band of 20 kDa under reduced conditions, whereas in the non-reducing conditions, it showed a band of 20 kDa and one additional band of 36 kDa. The average molecular mass determined by Electrospray Ionization Mass Spectrometry (ESI-MS) was 35.874 ± 2 Da in native and non-reducing conditions, whereas carboxyamidomethylated-lectin showed 18,111 Da. These data indicated that HiL consists in a dimer formed by identical subunits linked by disulfide bonds. Partial amino acid sequence of HiL was determined by mass spectrometry, and revealed that it is a new type of lectin, which showed no similarity with any protein. Secondary structure consisted of 6% α-helice, 31% ß-sheet, 18% ß-turn and 45% random coil. HiL showed significant reduction in the number of viable cells of Staphylococcus biofilms.
Subject(s)
Haliclona , Animals , Cattle , Swine , Haliclona/chemistry , Lectins/pharmacology , Spectrometry, Mass, Electrospray Ionization , Mucins , Biofilms , Molecular WeightABSTRACT
A new amide, baeriamide (1), along with nine known diketopiperazines (2-10), was isolated from the marine sponge Haliclona baeri. Their structures were identified by the means of UV, IR, MS and NMR. The absolute configuration of 1 was established by Marfey's method and comparing the specific optical rotation with the known compound HCO-Val-Gly methyl ester. Compound 1 was derived from dehydration of formylated L-valine with γ-amino-butanoic acid methyl ester. Compounds 2-10 were isolated from the genus of Haliclona for the first time. The absolute confirmation of 7 was confirmed first by the means of single-crystal X-ray diffraction. The cytotoxic, antibacterial, antiviral and antifouling activities of these compounds were also tested. However, none of them exhibited significant bioactivities.
Subject(s)
Haliclona , Animals , Haliclona/chemistry , Amides/pharmacology , Magnetic Resonance Spectroscopy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , DiketopiperazinesABSTRACT
Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1-8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Haliclona/chemistry , Isoquinolines/pharmacology , Active Transport, Cell Nucleus , Animals , Caco-2 Cells , Heme Oxygenase-1/genetics , Humans , Interferon-gamma/pharmacology , Isoquinolines/chemistry , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Structure-Activity Relationship , THP-1 CellsABSTRACT
Natural secondary metabolites of sponges of the genus Haliclona are associated with an array of biological activity with therapeutic usage. We investigated the immunopharmacological properties of a presumably novel marine sponge species from Sri Lanka, Haliclona (Soestella) sp. Sponge material was collected from southern Sri Lanka by scuba diving. Sponge identification was based on spicule and skeleton morphology using light microscopy. Selected in vivo and ex vivo tests investigated nonfunctional and functional immunomodulatory activity of the Haliclona (Soestella) sp. crude extract (HSCE) in the Wistar rat model. Compared to the controls, rats orally gavaged daily for 14 consecutive days with 15 mg/kg dose of the HSCE manifested a significant reduction of immune cell counts of total WBCs (by 17%; p < 0.01), lymphocytes (38%), platelets (52%), splenocytes (20%), and bone marrow cells (BMC; 60%) (p < 0.001), with a concurrent increase in the neutrophil : lymphocyte ratio (p < 0.05); RBC counts abated by 53% (p < 0.001). A significant reduction of the splenosomatic index was evident with the 10 and 15 mg/kg doses (p < 0.001). Rat plasma TNF-α cytokine level was augmented by tenfold (p < 0.001), IL-6 level by twofold (p < 0.01) with the 15 mg/kg HSCE treatment, while IL-10 was detectable in rat plasma only with this treatment; the corresponding Th1 : Th2 cytokine ratio (TNF-α : IL-10) was indicative of an unequivocal Th1-skewed cytokine response (p < 0.01). Ex vivo bone marrow cell and splenocyte proliferation were significantly and dose dependently impaired by HSCE (IC50 0.719 and 0.931 µg/mL, respectively; p < 0.05). Subacute toxicity testing established that HSCE was devoid of general toxic, hepatotoxic, and nephrotoxic effects. In conclusion, HSCE was orally active, nontoxic, and effectively suppressed nonfunctional and functional immunological parameters of Wistar rats, suggestive of the potential use of the HSCE as an immunosuppressant drug lead.
Subject(s)
Aquatic Organisms/chemistry , Biological Products/pharmacology , Cytokines/biosynthesis , Haliclona/chemistry , Immunomodulation/drug effects , Porifera/chemistry , Th1 Cells/drug effects , Th1 Cells/physiology , Animals , Biological Products/chemistry , Biological Products/isolation & purification , Male , Rats , Rats, Wistar , Sri LankaABSTRACT
An automated, high-capacity, and high-throughput procedure for the rapid isolation and identification of biologically active natural products from a prefractionated library is presented. The semipreparative HPLC method uses 1 mg of the primary hit fraction and produces 22 subfractions in an assay-ready format. Following screening, all active fractions are analyzed by NMR, LCMS, and FTIR, and the active principle structural classes are elucidated. In the proof-of-concept study, we show the processes involved in generating the subfractions, the throughput of the structural elucidation work, as well as the ability to rapidly isolate and identify new and biologically active natural products. Overall, the rapid second-stage purification conserves extract mass, requires much less chemist time, and introduces knowledge of structure early in the isolation workflow.
Subject(s)
Antineoplastic Agents/analysis , Biological Products/analysis , High-Throughput Screening Assays/methods , Small Molecule Libraries/analysis , Animals , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Biological Products/isolation & purification , Biological Products/pharmacology , Cell Line, Tumor , Chromatography, High Pressure Liquid , Drug Discovery , Gastropoda/chemistry , Haliclona/chemistry , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , National Cancer Institute (U.S.) , Proof of Concept Study , Small Molecule Libraries/isolation & purification , Small Molecule Libraries/pharmacology , Spectroscopy, Fourier Transform Infrared , United StatesABSTRACT
Marine sponges often house small-molecule-producing symbionts extracellularly in their mesohyl, providing the host with a means of chemical defence against predation and microbial infection. Here, we report an intriguing case of chemically mediated symbiosis between the renieramycin-containing sponge Haliclona sp. and its herein discovered renieramycin-producing symbiont Candidatus Endohaliclona renieramycinifaciens. Remarkably, Ca. E. renieramycinifaciens has undergone extreme genome reduction where it has lost almost all necessary elements for free living while maintaining a complex, multi-copy plasmid-encoded biosynthetic gene cluster for renieramycin biosynthesis. In return, the sponge houses Ca. E. renieramycinifaciens in previously uncharacterized cellular reservoirs (chemobacteriocytes), where it can acquire nutrients from the host and avoid bacterial competition. This relationship is highly specific to a single clade of Haliclona sponges. Our study reveals intracellular symbionts as an understudied source for defence chemicals in the oldest-living metazoans and paves the way towards discovering similar systems in other marine sponges.
Subject(s)
Gammaproteobacteria/physiology , Haliclona/chemistry , Haliclona/microbiology , Symbiosis , Tetrahydroisoquinolines/metabolism , Animals , Gammaproteobacteria/classification , Gammaproteobacteria/genetics , Gammaproteobacteria/metabolism , Genome Size , Haliclona/cytology , Haliclona/genetics , Host Specificity , Metagenome , Molecular Structure , Multigene Family , Phylogeny , Plasmids/genetics , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Symbiosis/genetics , Tetrahydroisoquinolines/chemistryABSTRACT
QM/NMR-DFT (quantum mechanics combined with nuclear magnetic resonance parameters calculated by density functional theory approximations) studies allowed us to link two stereoclusters separated by two methylene groups present in the new meroditerpenes halioxepine B (2) and halioxepine C (3) and the known halioxepine (1), isolated from two Indonesian sponges of the genus Haliclona (Reniera). DP4 and DP4+ probabilities were used to discriminate the two diastereotopic arrangements of the two stereoclusters, whose unconnected relative configurations were determined by ROESY and J-based configurational analysis. To confirm the DFT studies, the full relative configuration of 1 was deduced using a mixture of benzene-d6 and pyridine-d5 as the NMR solvent. ROESY measurements connected the two stereoclusters and demonstrated that DFT calculations accurately predict the configuration when two methylenes separate the two stereoclusters. The different arrangements of the distant stereoclusters C-1/C-2/C-7 and C-10/C-15 for compounds 2 and 3 were deduced by DFT calculations and explained the opposite optical rotations observed for the two compounds. Halioxepines B (2) and C (3) display moderate cytotoxicity against different human cancer cell lines.
Subject(s)
Cytotoxins/chemistry , Diterpenes/chemistry , Haliclona/chemistry , Porifera/chemistry , Animals , Cell Line, Tumor , Cytotoxins/pharmacology , Diterpenes/pharmacology , Humans , Indonesia , Magnetic Resonance Spectroscopy/methods , Quantum TheoryABSTRACT
Three new dimeric 3-alkyl pyridinium alkaloids, named haliclocyclamines A-C (1-3), were isolated together with five known congeners, cyclostellettamines A (4), B (5), C (6), E (7), and F (8), from the Indonesian marine sponge Haliclona sp. The structures of 1-3 were assigned based on their spectroscopic data (1D and 2D NMR, HRFABMS, ESIMS/MS, UV, and IR). Compounds 1-8 exhibited antimicrobial activities against Mycobacterium smegmatis with inhibition zones of 17, 10, 13, 14, 8, 8, 12, and 12mm, respectively, at 10µg/disc. Compounds 3 and 8 also modestly inhibited the activity of vaccinia H-1-related phosphatase (VHR), a dual-specificity phosphatase, at 17-18µM.
Subject(s)
Alkaloids/pharmacology , Anti-Bacterial Agents/pharmacology , Haliclona/chemistry , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium smegmatis/drug effects , Pyridinium Compounds/pharmacology , Alkaloids/chemistry , Alkaloids/isolation & purification , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Indonesia , Mycobacterium Infections, Nontuberculous/drug therapy , Pyridinium Compounds/chemistry , Pyridinium Compounds/isolation & purificationABSTRACT
Sarains are diamide alkaloids isolated from the Mediterranean sponge Haliclona (Rhizoniera) sarai that have previously shown antibacterial, insecticidal and anti-fouling activities. In this study, we examined for the first time the neuroprotective effects of sarains 1, 2 and A against oxidative stress in a human neuronal model. SH-SY5Y cells were co-incubated with sarains at concentrations ranging from 0.01 to 10 µM, and the well-known oxidant hydrogen peroxide at 150 µM for 6 h and the protective effects of the compounds were evaluated. Among the sarains tested, sarain A was the most promising compound, improving mitochondrial function and decreasing reactive oxygen species levels in human neuroblastoma cells treated with the compound at 0.01, 0.1 and 1 µM. This compound was also able to increase the activity of the antioxidant enzymes superoxide dismutases by inducing the translocation of the nuclear factor E2-related factor 2 (Nrf2) to the nucleus at the lower concentrations tested (0.01 and 0.1 µM). Moreover, sarain A at 0.1 and 1 µM blocked the mitochondrial permeability transition pore (mPTP) opening through cyclophilin D inhibition. These results suggest that the protective effects produced by the treatment with sarain A are related with its ability to block the mPTP and to enhance the Nrf2 pathway, indicating that sarain A may be a candidate compound for further studies in neurodegenerative diseases.
Subject(s)
Bridged-Ring Compounds/pharmacology , Hydrogen Peroxide/toxicity , Mitochondria/drug effects , Neurons/drug effects , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Adenosine Triphosphate/metabolism , Animals , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/pharmacology , Bridged-Ring Compounds/chemistry , Bridged-Ring Compounds/isolation & purification , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Cyclophilins/antagonists & inhibitors , Cyclophilins/metabolism , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Haliclona/chemistry , Humans , Hydrogen Peroxide/metabolism , Membrane Potential, Mitochondrial/drug effects , Membrane Potential, Mitochondrial/physiology , Mitochondria/physiology , Mitochondrial Diseases/chemically induced , Mitochondrial Diseases/drug therapy , Mitochondrial Diseases/metabolism , NF-E2-Related Factor 2/metabolism , Neurons/physiology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Oxidative Stress/physiology , Reactive Oxygen Species/metabolismABSTRACT
Twenty-eight sponge specimens were collected at a shallow water hydrothermal vent site north of Iceland. Extracts were prepared and tested in vitro for cytotoxic activity, and eight of them were shown to be cytotoxic. A mass spectrometry (MS)-based metabolomics approach was used to determine the chemical composition of the extracts. This analysis highlighted clear differences in the metabolomes of three sponge specimens, and all of them were identified as Haliclona (Rhizoniera) rosea (Bowerbank, 1866). Therefore, these specimens were selected for further investigation. Haliclona rosea metabolomes contained a class of potential key compounds, the 3-alkyl pyridine alkaloids (3-APA) responsible for the cytotoxic activity of the fractions. Several 3-APA compounds were tentatively identified including haliclamines, cyclostellettamines, viscosalines and viscosamines. Among these compounds, cyclostellettamine P was tentatively identified for the first time by using ion mobility MS in time-aligned parallel (TAP) fragmentation mode. In this work, we show the potential of applying metabolomics strategies and in particular the utility of coupling ion mobility with MS for the molecular characterization of sponge specimens.
Subject(s)
Alkaloids/toxicity , Hydrothermal Vents/chemistry , Metabolome/drug effects , Porifera/drug effects , Porifera/metabolism , Pyridines/toxicity , Alkaloids/chemistry , Animals , Haliclona/chemistry , Haliclona/metabolism , Iceland , Metabolomics/methods , Pyridines/chemistry , Pyridines/metabolism , Pyridinium Compounds/chemistry , Pyridinium Compounds/metabolism , Water/chemistryABSTRACT
The marine sponges Hyrtios and Haliclona species, both of which are known to produce secondary bioactive metabolites, were used to extract 1304KO-327 and 1304KO-328. Such secondary metabolites are potentially antibacterial, antiviral, anti-inflammatory, antitumoral, antifungal, and antiplasmodial. In the present study, the effects of 1304KO-327 and 1304KO-328 were studied for their clinical and pathological importance. The cytotoxicity of 1304KO-327 and 1304KO-328 was assessed via MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on HT-29, Caco-2, and Raw 264.7 cells. Rotavirus-infected Caco-2 cells were used to prove the antiviral effects of the marine sponge extracts. The test results cogently proved that the virus-inhibiting effects of the sponge extracts improved with extract concentration. Anti-inflammatory effects of the marine sponge extracts were tested on Lipopolysaccharide-treated Raw 264.7 cells. Nitric oxide and cytokine were produced by treatment of the cells with LPS and the inhibiting effects of the sponge extracts on IL-1ß formation were investigated. This study found that the NO production was decreased dose dependently, and IL-1ß formation was significantly reduced by the marine sponge extracts.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , Haliclona/chemistry , Porifera/chemistry , Rotavirus/drug effects , Animals , Caco-2 Cells , Cell Line, Tumor , Cytokines/immunology , Humans , Macrophages/drug effects , Macrophages/immunology , Mice , Nitric Oxide/immunology , RAW 264.7 Cells , Secondary MetabolismABSTRACT
A new alkaloid, 3-dodecyl pyridine containing a terminal cyano group (1), was isolated from the methanol extract of an Indonesia marine sponge Haliclona sp. Its chemical structure was determined by a combination of spectroscopic methods, including 1D and 2D NMR. Bioassay results indicated that compound 1 had moderate cytotoxity against tumour cell lines A549, MCF-7 and Hela with IC50 values of 41.8, 48.4 and 33.2 µM, respectively.
Subject(s)
Alkaloids/chemistry , Antineoplastic Agents/isolation & purification , Haliclona/chemistry , Alkaloids/toxicity , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Humans , Indonesia , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Porifera/chemistry , Pyridines/isolation & purificationABSTRACT
The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avendaño's protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5-trimethylphenyl)methyl-piperazine-2,5-dione (8) in 18 steps (8.3% overall yield). The synthesis provides unambiguous evidence supporting the original structure of renieramycin I.
Subject(s)
Isoquinolines/chemistry , Tetrahydroisoquinolines/chemistry , Animals , Benzoquinones/chemistry , Haliclona/chemistry , Piperazine , Piperazines/chemistry , Selenium Oxides/chemistry , StereoisomerismABSTRACT
Three new polyunsaturated lipids, (6Z,9Z,12Z,15Z)-octadeca-6,9,12,15-tetraen-3-one (1), (6Z,9Z,12Z,15Z)-1-bromooctadeca-6,9,12,15-tetraen-3-one (2), and (Z)-ethyl docos-5-enoate (3), together with two known polyunsaturated lipids, 4(Z),7(Z),10(Z)-tridecatrienoic acid (4) and (6Z,9Z,12Z,15Z)-octadeca-1,6,9,12,15-pentaen-3-one (5), were isolated from the marine sponge Haliclona sp., which was collected from Guangxi, using HSCCC and HPLC methods. Chemical structures of the five compounds were elucidated by spectroscopic techniques.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Fatty Acids, Unsaturated/isolation & purification , Haliclona/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , China , Chromatography, High Pressure Liquid , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/pharmacology , Macrophages , Marine Biology , Mice , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , StereoisomerismABSTRACT
A new chromophore-containing agglutinin (Haliclona manglaris agglutinin (HMA)) was isolated from the tropical sponge H. manglaris. HMA was purified by a combination of hydrophobic interaction chromatography and ion exchange chromatography. Native HMA is a heterotrimer formed by two ß-chains (15 kDa) and one α-chain (22 kDa). HMA is a glycoprotein and possesses three intrachain disulfide bonds. Hemagglutinating activity of HMA was stable at neutral pH and temperatures up to 60 °C. HMA was only inhibited by thyroglobulin. Mass spectrometry sequencing and Edman degradation revealed a unique amino acid sequence of about 30%. Moreover, HMA has an organic chromophore of 581 Da, and this characteristic seems to be important to its antioxidant activity. Interestingly, while HMA showed no toxicity against Artemia nauplii and was unable to agglutinate bacterial cells, it did show a high capacity to protect ß-carotene against oxidation. Thus, our findings suggest the putative involvement of HMA in the protection of the sponge against oxidation.
Subject(s)
Agglutinins/chemistry , Agglutinins/isolation & purification , Fluorescent Dyes/chemistry , Haliclona/chemistry , Amino Acid Sequence , Animals , Antioxidants/pharmacology , Artemia/drug effects , Carbohydrates/analysis , Cations, Divalent/pharmacology , Chromatography, Gel , Chromatography, Reverse-Phase , Electrophoresis, Polyacrylamide Gel , Hemagglutination/drug effects , Hydrogen-Ion Concentration , Molecular Sequence Data , Molecular Weight , Peptides/chemistry , Rabbits , Sequence Analysis, Protein , Sulfhydryl Compounds/chemistry , Tandem Mass Spectrometry , TemperatureABSTRACT
AIMS: Sessile marine invertebrates engage in a diverse array of beneficial interactions with bacterial symbionts. One feature of some of these relationships is the presence of bioactive natural products that can defend the holobiont from predation, competition or disease. In this study, we investigated the antimicrobial activity and microbial community of a common temperate sponge from coastal North Carolina. METHODS AND RESULTS: The sponge was identified as a member of the genus Haliclona, a prolific source of bioactive natural products, based on its 18S rRNA gene sequence. The crude chemical extract and methanol partition had broad activity against the assayed Gram-negative and Gram-positive pathogenic bacteria. Further fractionation resulted in two groups of compounds with differing antimicrobial activity, primarily against Gram-positive test organisms. There was, however, notable activity against the Gram-negative marine pathogen, Vibrio parahaemolyticus. Microbial community analysis of the sponge and surrounding sea water via denaturing gradient gel electrophoresis (DGGE) indicates that it harbours a distinct group of bacterial associates. CONCLUSIONS: The common temperate sponge, Haliclona sp., is a source of multiple antimicrobial compounds and has some consistent microbial community members that may play a role in secondary metabolite production. SIGNIFICANCE AND IMPACT OF THE STUDY: These data suggest that common temperate sponges can be a source of bioactive chemical and microbial diversity. Further studies may reveal the importance of the microbial associates to the sponge and natural product biosynthesis.
Subject(s)
Anti-Bacterial Agents/pharmacology , Haliclona/microbiology , Animals , Anti-Bacterial Agents/isolation & purification , Bacteria/genetics , Bacteria/isolation & purification , Haliclona/chemistry , Haliclona/genetics , Seawater/microbiologyABSTRACT
The Mediterranean dorid nudibranch Peltodoris atromaculata that had been collected while feeding on Haliclona fulva was shown to sequester long-chain fulvinol-like polyacetylene metabolites (compounds 2-5) from the prey. They were isolated along with previously reported bromorenierins from the diethyl ether extracts of both the mollusk and the sponge. Their structures were elucidated by NMR spectroscopy and tandem FABMS analysis. Compound 5 exhibited in vitro growth inhibitory effects against the SKMEL-28 melanoma cell line.
Subject(s)
Antineoplastic Agents/isolation & purification , Gastropoda/chemistry , Haliclona/chemistry , Polyynes/isolation & purification , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Polyynes/chemistry , Polyynes/pharmacologyABSTRACT
In this study, antifungal and antibacterial activities of diethyl ether, methanol and aqueous extracts of Haliclona sp. were assessed (in vitro). The antibacterial activity of the extracts was determined by broth dilution methods against clinical Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa and Gram-positive bacteria: Staphylococcus aureus aureus, Bacillus subtilis spizizenii. The antifungal activity of the extracts was determined by using a broth microdilution test against clinical fungi Candida albicans and Aspergillus fumigatus. Our results showed diethyl ether extract of Haliclona sp. was active on Gram-positive bacteria. In addition, methanol extract in comparison with diethyl ether extract had better activity against C. albicans (MIC: 0.75 mg/mL, MFC: 1.5mg/mL) and A. fumigatus (MIC: 2mg/mL, MFC: 3mg/mL). Aqueous extract had neither antifungal nor antibacterial activities. Based our results, Haliclona sp. can be considered as a source of novel antibiotic and antifungal.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Haliclona , Animals , Anti-Bacterial Agents/isolation & purification , Antifungal Agents/isolation & purification , Aspergillus fumigatus/drug effects , Aspergillus fumigatus/growth & development , Bacillus subtilis/drug effects , Bacillus subtilis/growth & development , Candida albicans/drug effects , Candida albicans/growth & development , Cell Extracts/pharmacology , Haliclona/chemistry , Humans , Indian Ocean , Iran , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & developmentABSTRACT
LiNH2BH3-promoted reductive opening of 8-substituted phenylglycinol-derived oxazolopiperidone lactams leads to enantiopure 4-substituted-5-aminopentanols, which are used as starting building blocks in the synthesis of the Haliclona alkaloids haliclorensin C, haliclorensin, and halitulin (formal). The starting lactams are easily accessible by a cyclocondensation reaction of (R)-phenylglycinol with racemic γ-subtituted δ-oxoesters, in a process that involves a dynamic kinetic resolution.