RESUMO
UNLABELLED: Sponges are a rich source for investigation of bioactive small molecules. They have been mostly investigated for the search of new pharmacological models or therapeutic agents for the treatment of human diseases. Micro-organisms can also represent a virulent pathogen for marine invertebrates such as sponges, which need to protect themselves against these microbes. Sponges' self defence mechanisms involving dialogue molecules thus represent a pertinent research track for potent anti-infective and anti-biofilm activities such as quorum sensing inhibitors (QSIs). The investigation of the QSI crude extract of Leucetta chagosensis Dendy, 1863 led to the isolation of three new alkaloids, isonaamine D, di-isonaamidine A and leucettamine D, along with the known isonaamine A and isonaamidine A. Isonaamidine A and isonaamine D were identified as inhibitors of the three quorum sensing pathways of Vibrio harveyi (CAI-1, AI-2 and harveyi auto inducer), but isonaamidine A displayed the strongest activity on AI-2 biosensor. Both compounds are new examples of natural QSIs of V. harveyi. These results outline the importance of these secondary metabolites for their producing organisms themselves in their natural environment, as well as the potential of the marine resource for aquaculture needs. SIGNIFICANCE AND IMPACT OF THE STUDY: A new type of quorum sensing inhibitors was isolated from the sponge Leucetta chagosensis. One of them inhibits strongly the AI-2 channel of Vibrio harveyi, a marine pathogen of special importance in aquaculture. The activity of five different related compounds, including three new natural products discovered there, was investigated leading to structure-activity relationships which are useful for the design of new quorum sensing inhibitors to control marine infectious pathogens.
Assuntos
Alcaloides/farmacologia , Biofilmes/efeitos dos fármacos , Incrustação Biológica/prevenção & controle , Imidazóis/farmacologia , Poríferos/química , Percepção de Quorum/efeitos dos fármacos , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Aquicultura , Imidazóis/química , Imidazóis/isolamento & purificação , Relação Estrutura-Atividade , Vibrio/efeitos dos fármacos , Vibrio/fisiologiaRESUMO
The compound haliclonacyclamine A was isolated from the Haliclona sponge at Solomon Islands. It acts as a powerful in vitro and in vivo anti-plasmodial agent against the chloroquine-resistant Plasmodium falciparum strain FCB1and Plasmodium vinckei petteri-infected mice, respectively.
Assuntos
Haliclona/química , Compostos Macrocíclicos/farmacologia , Malária/tratamento farmacológico , Piperidinas/farmacologia , Plasmodium/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Compostos Macrocíclicos/química , Compostos Macrocíclicos/isolamento & purificação , Compostos Macrocíclicos/uso terapêutico , Espectroscopia de Ressonância Magnética , Melanesia , Camundongos , Estrutura Molecular , Piperidinas/química , Piperidinas/isolamento & purificação , Piperidinas/uso terapêutico , Análise de SobrevidaRESUMO
A new diterpene, N-formyl-7-amino-11-cycloamphilectene (1), was isolated from the apolar extract of the Vanuatu sponge Axinella sp. The structure and relative stereochemistry were established by spectroscopic and single-crystal X-ray studies.
Assuntos
Diterpenos/isolamento & purificação , Poríferos/química , Animais , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Diterpenos/química , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo , VanuatuRESUMO
Two new metabolites, named halipeptins A and B, have been isolated from the marine sponge Haliclona sp. Their structures were determined by extensive use of one- and two-dimensional NMR experiments, mass spectrometry, and UV and IR spectroscopy. Halipeptin A is a novel 17-membered cyclic depsipeptide, consisting of five residues including two alanines (with L stereochemistry) and three new residues that appear to be previously undescribed from natural sources: 1,2-oxazetidine-4-methyl-4-carboxylic acid, 3-hydroxy-2,2,4-trimethyl-7-methoxydecanoic acid (HTMMD), and N-methyl-delta-hydroxyisoleucine. The HTMMD residue is substituted with 3-hydroxy-2,2,4-trimethyl-7-hydroxydecanoic acid in halipeptin B. Halipeptin A was found to possess very potent anti-inflammatory activity in vivo, causing about 60% inhibition of edema in mice at the dose of 300 microg/kg (i.p.).
Assuntos
Anti-Inflamatórios não Esteroides/química , Depsipeptídeos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Poríferos/química , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Humanos , Leucemia L1210/tratamento farmacológico , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/farmacologia , Conformação Proteica , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Estereoisomerismo , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
A new pyrroloiminoquinone alkaloid (1) belonging to the makaluvamine family has been isolated from the sponge Zyzzya cf. fuliginosa collected in the waters off the Vanuatu Islands. The compound, designated makulavamine P, was characterized on the basis of its spectral data and displayed cytoxicity in the microM range on KB cells and antioxidant activity.
Assuntos
Antineoplásicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Poríferos/química , Pirróis/isolamento & purificação , Quinolonas/isolamento & purificação , Xantina Oxidase/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Austrália , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Células KB/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Neoplasias Nasofaríngeas , Pirróis/química , Pirróis/farmacologia , Quinolonas/química , Quinolonas/farmacologia , Testes de Toxicidade , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
The dual specificity CDC25 phosphatases dephosphorylate two inhibitory phospho-amino acids of cyclin-dependent kinases, a major family of cell cycle regulators. CDC25 inhibitors constitute new anti-mitotic agents with potential anticancer activity. While screening through a collection of natural products derived from marine organisms for CDC25A inhibitors, we purified and identified coscinosulfate 1, a sesquiterpene sulfate from the New Caledonian sponge Coscinoderma matthewsi, along with 4. The purified compound 1 displayed significant inhibitory activity towards CDC25A (IC(50): 3 microM).
Assuntos
Antineoplásicos/isolamento & purificação , Poríferos/química , Terpenos/isolamento & purificação , Fosfatases cdc25/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Proteínas Recombinantes de Fusão/antagonistas & inibidores , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Terpenos/química , Terpenos/farmacologiaRESUMO
The effects of gymnochrome A were tested on the electrical activity of the frog atrial heart muscle. Gymnochrome A (1-5 microM) did not alter the resting potential. Gymnochrome A (5 microM) slowed the initial depolarizing phase of the spontaneously beating action potential. Under voltage-clamp conditions gymnochrome A (5 microM) did not affect the electrical constant of the membrane and the kinetic parameters of the peak Na+ current (INa) recorded in the Ringer solution containing tetraethylammonium (2 mM) and Cd2+ (1 mM) but shifted the membrane potential at which the current both activated and reached its maximal value toward more negative membrane potentials. It did not alter the reversal potential for INa, indicating that the selectivity of the Na+ channels had not changed. These observations suggest that gymnochrome A binds to the membrane and shifts the activation of INa on the voltage axis by modifying the free negative fixed charges present at the membrane surface rather than by occupying a specific site on the Na+ channel. Photoexcited gymnochrome A transiently triggered an early outward current which lengthened the time-to-peak of INa and decreased its amplitude. In addition, photoexcited gymnochrome A blocked the background K+ current. This is, to our knowledge, the first time that such effects are reported on the cardiac muscle. These observations suggest that the photoexcitation of gymnochrome produces physico-chemical effects which lead to intracellular changes. Further experiments are required to determine their nature.
Assuntos
Coração/efeitos dos fármacos , Miocárdio/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Quinonas/farmacologia , Animais , Equinodermos , Técnicas In Vitro , Potenciais da Membrana/efeitos dos fármacos , Fotoquímica , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Hidrocarbonetos Policíclicos Aromáticos/efeitos da radiação , Quinonas/isolamento & purificação , Quinonas/efeitos da radiação , Rana esculenta , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/metabolismoRESUMO
Two new sesquiterpene cyclopentenones, dysidenones A and B (2, 3), and a new sesquiterpene aminoquinone, dysidine (4), all containing the same rearranged drimane skeleton, have been isolated from a Dysidea sp. sponge, along with bolinaquinone (1). The structures were established from 2D NMR data. Bolinaquinone (1), dysidine (4), and a 1:1 mixture of dysidenones A and B (2, 3) significantly inhibited human synovial phospholipase A2 (PLA2) at 10 microM. Compound 4, which shows an IC50 value of 2.0 microM, exerts a higher potency and selectivity toward this enzyme than the reference inhibitor manoalide. In addition, all of these compounds modulated at 10 microM other human leukocyte functions such as the degranulation process measured as elastase release and the superoxide production measured by chemiluminescence.
Assuntos
Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Leucócitos/efeitos dos fármacos , Fosfolipases A/antagonistas & inibidores , Poríferos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Animais , Degranulação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Humanos , Elastase de Leucócito/antagonistas & inibidores , Medições Luminescentes , Espectroscopia de Ressonância Magnética , Fosfolipases A2 , Espectrofotometria UltravioletaRESUMO
Six new cytotoxic isomalabaricane-type triterpenoids and nortriterpenoids with a 3alpha-acetoxy group were isolated, along with the known globostellatic acids B (1) and C (2), from the marine sponge Jaspis sp. collected at Vanuatu Island. The structures were determined by 2D NMR data and by comparison with spectral data of known related compounds.
Assuntos
Poríferos/química , Animais , Estrutura Molecular , Análise EspectralRESUMO
[structure: see text] The C-glycoconjugate C(2)-alpha-D-mannosylpyranosyl-L-tryptophan (1), a metabolite known to be generated in humans through a novel posttranslational process, has been isolated from marine ascidians Leptoclinides dubius and Pharyngodictyon cauliflos and its N(alpha)-methyl derivative (2) from Ritterella rete.
Assuntos
Triptofano/análogos & derivados , Triptofano/isolamento & purificação , Urocordados/química , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Ressonância Magnética Nuclear Biomolecular , Triptofano/química , Urocordados/metabolismoRESUMO
Four new bioactive pyridinium alkaloids, named spongidines A-D (5-8), have been isolated from a Vanuatu sponge of the genus Spongia, together with known petrosaspongiolides D (1) and G (2). Compounds 3 and 4 are 21-hydroxy derivatives of petrosaspongiolides K and P. Structure elucidation was accomplished through extensive 2D NMR experiments (COSY, ROESY, HMBC, HMQC) and IR, UV, and FABMS data. All compounds significantly inhibited human synovial phospholipase A(2) (PLA(2)) at 10 microM, with an IC(50) value of 5.8 microM for compound 4, which is the most potent inhibitor, with a higher selectivity toward this enzyme than the reference inhibitor manoalide. Pyridinium alkaloids (5-8) mainly inhibited human synovial PLA(2). Compound 8, which contains a sulfonic acid group, is the most interesting inhibitor.
Assuntos
Alcaloides/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Fosfolipases A/antagonistas & inibidores , Poríferos/química , Alcaloides/química , Alcaloides/farmacologia , Animais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Estrutura Molecular , Compostos de Piridínio/química , Análise EspectralRESUMO
: Quinolones and a phosphatidyl glyceride were isolated from the sponge-associated bacterial strain Pseudomonas sp. Structures were elucidated by spectroscopic analysis and chemical transformations.
RESUMO
Two new jaspamide derivatives (1 and 2) along with jaspamide have been isolated from the marine sponge Jaspis splendans collected in Vanuatu. Their chemical structures were determined from 1D and 2D NMR studies and MS data. These two compounds inhibited the in vitro growth of the NSCLC-N6 human tumor cell lines with IC50 values in the microg/mL range.
Assuntos
Antineoplásicos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Poríferos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Divisão Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/patologia , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Análise Espectral , Células Tumorais CultivadasRESUMO
A marine bacterium, identified as a pseudomonad, isolated from Suberea creba Bergquist, 1995 (Porifera, Dictyoceratida, Verongida, Aplysinellidae) collected along the eastern coast of New Caledonia, gave in culture phenazine-alpha-carboxamide, 2-n-heptylquinol-4-one, 2-n-nonylquinol-4-one, 2-n-(1'E-nonenyl)quinol-4-one, 3-n-heptyl-3-hydroxyquinolin-2,4-dione, a N-oxide-2-n-heptylquinoline derivative, and a benzyldiketopiperazine. None of these products could be detected, at the HPLC-UV sensitivity level, in the sponge extracts, which contained instead (+)-aerothionin, homoaerothionin, (+)-aeroplysinin-1, dibromo-, bromochloro-, and dichloroverongiaquinol. 2-n-Heptylquinol-4-one, (+)-aeroplysinin-1, and dibromoverongiaquinol showed strong antibacterial activity in vitro. The latter also proved promising for mariculture, rivaling chloramphenicol as an antibacterial agent in cultures of Pecten maximus larvae, while being nontoxic according to the Artemia salina test.
RESUMO
Five new bioactive sesterterpenes (1-5) have been isolated from the New Caledonian marine sponge Petrosaspongia nigra Bergquist and named petrosaspongiolides M-R. Their chemical structures were determined from 1D and 2D NMR studies and MS data. All compounds inhibited different preparations of phospholipase A2 (PLA2) by irreversibly blocking these enzymes (particularly human synovial and bee venom, see Table 3), with IC50 values in the micromolar range. Interestingly, these compounds displayed a much lower activity (or no activity at all) toward porcine pancreas and Naja naja venom PLA2 enzymes. The most potent compound, 1 (IC50 1.6 and 0.6 microM for human synovial and bee venom PLA2 enzymes, respectively), was slightly more active than manoalide (6) (IC50 3.9 and 7.5 microM) under our experimental conditions. Compound 3 is more selective, inhibiting human synovial PLA2 to a greater extent than bee venom PLA2.
Assuntos
4-Butirolactona/análogos & derivados , Inibidores Enzimáticos/isolamento & purificação , Fosfolipases A/antagonistas & inibidores , Poríferos/química , Terpenos/isolamento & purificação , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Animais , Venenos de Abelha/enzimologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pâncreas/enzimologia , Fosfolipases A2 , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Suínos , Líquido Sinovial/enzimologia , Terpenos/química , Terpenos/farmacologiaRESUMO
Metabolites isolated from marine invertebrates, callipeltin A, crambescidin, ptilomycalin A, celeromycalin, gymnochrome B, gymnochrome D and isogymnochrome D previously shown bioactive on either herpes simplex virus 1 or human immunodeficiency virus, were tested on a new in vitro bioassay using the dengue virus 1. Only gymnochrome D and isogymnochrome D isolated from the living fossil crinoid Gymnocrinus richeri are highly potent dengue antiviral agents.
Assuntos
Antivirais/química , Vírus da Dengue/efeitos dos fármacos , Dengue/tratamento farmacológico , Equinodermos/química , Poríferos/química , Animais , Células Cultivadas , Estrutura Molecular , Ensaio de Placa ViralRESUMO
In an ongoing survey of the bioactive potential of microorganisms associated with marine invertebrates, the extract of the sponge-associated bacterial strain Micrococcus luteus was found to exhibit potent antimicrobial activity. The previously known synthetic 2,4,4'-trichloro-2'-hydroxydiphenylether was found to be responsible for the antimicrobial activity. The major metabolite isolated was a new acyl-1-(acyl-6'-mannobiosyl)-3-glycerol.
RESUMO
The vasoactive intestinal peptide (VIP) and somatostatin (somatotropin release inhibiting factor, SRIF) are important neurotransmitters in a number of basic physiological events. Their disturbances have been reported in many diseases such as cystic fibrosis, impotent man (VIP), Alzheimer's disease, and some tumours (SRIF). Xestospongine B (1), sceptrine (2), and ageliferine (3), three alkaloids isolated from Xestospongia sp. and Agelas novaecaledoniae are reported as somatostatin and VIP inhibitors. The natural products 1, 2 and 3 exhibited a high affinity for somatostatin (IC50 = 12 microM, 0.27 microM, and 2.2 microM, respectively), 2 and 3 showed an affinity for VIP (19.8 microM and 19.2 microM, respectively). Due to the interaction between non-peptidic compounds and somatostatin/VIP receptors, these three alkaloids could be promising agents in the research on natural non-peptidic compounds for therapeutical interventions.
Assuntos
Alcaloides/farmacologia , Poríferos/química , Somatostatina/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
A novel cyclodepsipeptide, neosiphoniamolide A [1], has been isolated from the sponge Neosiphonia superstes. The structure of 1, which contains a 12-carbon hydroxy acid, glycine, valine, and a halogenated tyrosine residue in an 18-membered ring, is related to jaspamide and the geodiamolides, previously isolated from sponges. The structure was solved by spectroscopic analysis.
Assuntos
Antifúngicos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Poríferos/química , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologiaRESUMO
The structure of a new cytotoxic macrolide, superstolide B [1], isolated from the deep water sponge Neosiphonia superstes, collected off New Caledonia, was elucidated mainly on the basis of nmr data. Compound 1 is closely related to superstolide A [2], a major cytotoxic component isolated from that organism, but lacks the 25-hydroxyl group found in 2 and has a C-24 (C-25)-double bond.