RESUMO
Assimiloside A (1), an unprecedented marine glycolipid containing a γ-lactone of 4R,16,26R-trihydroxy C28 fatty acid as an aglycon and a trisaccharide carbohydrate moiety, was isolated from the marine sponge Hymeniacidon assimilis. Its structure was elucidated by NMR spectroscopy, mass spectrometry, chemical transformations, and ECD spectroscopy combined with time-dependent density functional theory calculations. Assimiloside A at nontoxic concentrations of 0.01-0.1 µM was shown to present lysosomal activity stimulation and intracellular reactive oxygen species level elevation in RAW 264.7 murine macrophages.
Assuntos
Glicolipídeos , Poríferos , Animais , Camundongos , Glicolipídeos/farmacologia , Poríferos/química , Espectroscopia de Ressonância Magnética , Ácidos Graxos , Estrutura MolecularRESUMO
Three new tetrasulfated triterpene glycosides, chilensosides E (1), F (2), and G (3), have been isolated from the Far-Eastern sea cucumber Paracaudina chilensis (Caudinidae, Molpadida). The structures were established based on extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The compounds differ in their carbohydrate chains, namely in the number of monosaccharide residues (five or six) and in the positions of sulfate groups. Chilensosides E (1) and F (2) are tetrasulfated pentaosides with the position of one of the sulfate groups at C-3 Glc3, and chilensoside G (3) is a tetrasulfated hexaoside. The biogenetic analysis of the glycosides of P. chilensis has revealed that the structures form a network due to the attachment of sulfate groups to almost all possible positions. The upper semi-chain is sulfated earlier in the biosynthetic process than the lower one. Noticeably, the presence of a sulfate group at C-3 Glc3-a terminal monosaccharide residue in the bottom semi-chain of compounds 1 and 2-excludes the possibility of this sugar chain's further elongation. Presumably, the processes of glycosylation and sulfation are concurrent biosynthetic stages. They can be shifted in time in relation to each other, which is a characteristic feature of the mosaic type of biosynthesis. The hemolytic action of compounds 1-3 against human erythrocytes and cytotoxic activities against five human cancer cell lines were tested. The compounds showed moderate hemolytic activity but were inactive against cancer cells, probably because of their structural peculiarities, such as the combination of positions of four sulfate groups.
Assuntos
Pepinos-do-Mar , Triterpenos , Animais , Humanos , Glicosídeos/química , Pepinos-do-Mar/química , Triterpenos/química , Linhagem Celular Tumoral , Hemólise , Sulfatos , Estrutura MolecularRESUMO
Toporosides A-D (1-4), new ω-glycosylated fatty acid amides, were isolated from the sponge Stelodoryx toporoki. The structures of these compounds, including absolute configurations of stereogenic centers, were established using analysis of 1D and 2D NMR, ECD, and HR mass spectra as well as chemical transformations. Toporosides A (1) and B (2) are the first lipids containing a cyclopentenyl α,ß-unsaturated carbonyl moiety in the polymethylene chain. Toporoside C (3) is likely a precursor, which undergoes intramolecular aldol condensation to produce 1 and 2. Toporosides A, C, and D showed protective effects against TNF-α-induced injury in H9c2 cardiomyocytes.
Assuntos
Amidas , Poríferos , Amidas/química , Animais , Ácidos Graxos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Poríferos/químicaRESUMO
Five new triterpene (4,4,14-trimethylsterol) di-, tri- and tetrasulfated pentaosides, chilensosides A (1), A1 (2), B (3), C (4), and D (5) were isolated from the Far-Eastern sea cucumber Paracaudina chilensis. The structures were established on the basis of extensive analysis of 1D and 2D NMR spectra and confirmed by HR-ESI-MS data. The structural variability of the glycosides concerned the pentasaccharide chains. Their architecture was characterized by the upper semi-chain consisting of three sugar units and the bottom semi-chain of two sugars. Carbohydrate chains of compounds 2-5 differed in the quantity and positions of sulfate groups. The interesting structural features of the glycosides were: the presence of two sulfate groups at C-4 and C-6 of the same glucose residue in the upper semi-chain of 1, 2, 4, and 5 and the sulfation at C-3 of terminal glucose residue in the bottom semi-chain of 4 that makes its further elongation impossible. Chilensoside D (5) was the sixth tetrasulfated glycoside found in sea cucumbers. The architecture of the sugar chains of chilensosides A-D (1-5), the positions of sulfation, the quantity of sulfate groups, as well as the aglycone structures, demonstrate their similarity to the glycosides of the representatives of the order Dendrochirotida, confirming the phylogenetic closeness of the orders Molpadida and Dendrochirotida. The cytotoxic activities of the compounds 1-5 against human erythrocytes and some cancer cell lines are presented. Disulfated chilensosides A1 (2) and B (3) and trisulfated chilensoside C (4) showed significant cytotoxic activity against human cancer cells.
Assuntos
Antineoplásicos , Neoplasias , Pepinos-do-Mar , Triterpenos , Animais , Humanos , Pepinos-do-Mar/química , Triterpenos/farmacologia , Triterpenos/química , Filogenia , Glicosídeos/farmacologia , Glicosídeos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Açúcares , Sulfatos , Glucose , Estrutura MolecularRESUMO
Fucosylated chondroitin sulfates (FCSs) PC and HH were isolated from the sea cucumbers Paracaudina chilensis and Holothuria hilla, respectively. The purification of the polysaccharides was carried out by anion-exchange chromatography on a DEAE-Sephacel column. The structural characterization of the polysaccharides was performed in terms of monosaccharide and sulfate content, as well as using a series of nondestructive NMR spectroscopic methods. Both polysaccharides were shown to contain a chondroitin core [â3)-ß-d-GalNAc (N-acethyl galactosamine)-(1â4)-ß-d-GlcA (glucuronic acid)-(1â]n, bearing sulfated fucosyl branches at O-3 of every GlcA residue in the chain. These fucosyl residues were different in their pattern of sulfation: PC contained Fuc2S4S and Fuc4S in a ratio of 2:1, whereas HH included Fuc2S4S, Fuc3S4S, and Fuc4S in a ratio of 1.5:1:1. Moreover, some GalNAc residues in HH were found to contain an unusual disaccharide branch Fuc4S-(1â2)-Fuc3S4S-(1â at O-6. Sulfated GalNAc4S6S and GalNAc4S units were found in a ratio of 3:2 in PC and 2:1 in HH. Both polysaccharides demonstrated significant anticoagulant activity in a clotting time assay, which is connected with the ability of these FCSs to potentiate the inhibition of thrombin and factor Xa in the presence of anti-thrombin III (ATIII) and with the direct inhibition of thrombin in the absence of any cofactors.
Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Sulfatos de Condroitina/farmacologia , Holothuria/metabolismo , Animais , Anticoagulantes/isolamento & purificação , Antitrombina III/metabolismo , Antitrombinas/isolamento & purificação , Antitrombinas/farmacologia , Sulfatos de Condroitina/isolamento & purificação , Fator Xa/metabolismo , Inibidores do Fator Xa/isolamento & purificação , Inibidores do Fator Xa/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade , Trombina/antagonistas & inibidores , Trombina/metabolismoRESUMO
Seven new polyoxygenated steroids belonging to a new structural group of sponge steroids, gracilosulfates A-G (1-7), possessing 3ß-O-sulfonato, 5ß,6ß epoxy (or 5(6)-dehydro), and 4ß,23-dihydroxy substitution patterns as a common structural motif, were isolated from the marine sponge Haliclona gracilis. Their structures were determined by NMR and MS methods. The compounds 1, 2, 4, 6, and 7 inhibited the expression of prostate-specific antigen (PSA) in 22Rv1 tumor cells.
Assuntos
Antineoplásicos/farmacologia , Haliclona/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Esteroides/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Calicreínas/metabolismo , Masculino , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Esteroides/química , Esteroides/isolamento & purificaçãoRESUMO
Leptogorgins A-C (1-3), new humulane sesquiterpenoids, and leptogorgoid A (4), a new dihydroxyketosteroid, were isolated from the gorgonian Leptogorgia sp. collected from the South China Sea. The structures were established using MS and NMR data. The absolute configuration of 1 was confirmed by a modification of Mosher's method. Configurations of double bonds followed from NMR data, including NOE correlations. This is the first report of humulane-type sesquiterpenoids from marine invertebrates. Sesquiterpenoids leptogorgins A (1) and B (2) exhibited a moderate cytotoxicity and some selectivity against human drug-resistant prostate cancer cells 22Rv1.
Assuntos
Antozoários/química , Sesquiterpenos/química , Animais , Organismos Aquáticos , Água do Mar , VietnãRESUMO
Two novel C19 terpenoids (1, 2) with an unprecedented carbon skeleton (A) were isolated from a Stelletta sp. sponge collected from Vietnamese waters. Their structures and absolute configurations were established by extensive NMR, MS, and ECD analyses together with quantum chemical modeling and biogenetic considerations. The probable pathways of biogenesis of 1 and 2 from isomalabaricane triterpenoids are discussed. Compounds 1 and 2 significantly increase the production of reactive oxygen species in murine peritoneal macrophages.
Assuntos
Poríferos/química , Terpenos/química , Terpenos/farmacologia , Animais , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Estrutura Molecular , Poríferos/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Guitarrins A-E (1-5), the first natural 5-azaindoles, and aluminumguitarrin A (1a), the first aluminum-containing compound from marine invertebrates, were isolated from the sponge Guitarra fimbriata. The structures of these compounds were established using detailed analysis of 1D and 2D NMR data, mass spectra, and X-ray analysis of 1 and 1a. Compound 3 was proved to be a natural inhibitor of alkaline phosphatase.
Assuntos
Compostos de Alumínio/farmacologia , Compostos Aza/farmacologia , Indóis/farmacologia , Poríferos/química , Compostos de Alumínio/química , Compostos de Alumínio/isolamento & purificação , Animais , Compostos Aza/química , Compostos Aza/isolamento & purificação , Indóis/química , Indóis/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura MolecularRESUMO
Glycoconjugated and other polar steroids of starfish have unique chemical structures and show a broad spectrum of biological activities. However, their biological functions remain not well established. Possible biological roles of these metabolites might be indicated by the studies on their distribution in the organism-producer. In order to investigate the localization of polar steroids in body components of the Far Eastern starfish Lethasterias fusca, chemical constituents of body walls, gonads, stomach, pyloric caeca, and coelomic fluid were studied by nanoflow liquid chromatography/mass spectrometry with captive spray ionization (nLC/CSI-QTOF-MS). It has been shown that the levels of polar steroids in the studied body components are qualitatively and quantitatively different. Generally, the obtained data confirmed earlier made assumptions about the digestive function of polyhydroxysteroids and protective role of asterosaponins. The highest level of polar steroids was found in the stomach. Asterosaponins were found in all body components, the main portion of free polyhydroxysteroids and related glycosides were located in the pyloric caeca. In addition, a great inter-individual variability was found in the content of most polar steroids, which may be associated with the peculiarities in their individual physiologic status.
Assuntos
Glicosídeos/metabolismo , Hidroxiesteroides/metabolismo , Saponinas/metabolismo , Estrelas-do-Mar/metabolismo , Animais , Cromatografia Líquida/métodos , Esteroides/metabolismo , Estômago/fisiologia , Espectrometria de Massas em Tandem/métodosRESUMO
Seven new unusual polysulfated steroids-topsentiasterol sulfate G (1), topsentiasterol sulfate I (2), topsentiasterol sulfate H (3), bromotopsentiasterol sulfate D (4), dichlorotopsentiasterol sulfate D (8), bromochlorotopsentiasterol sulfate D (9), and 4ß-hydroxyhalistanol sulfate C (10), as well as three previously described-topsentiasterol sulfate D (7), chlorotopsentiasterol sulfate D (5) and iodotopsentiasterol sulfate D (6) have been isolated from the marine sponge Halichondria vansoesti. Structures of these compounds were determined by detailed analysis of 1D- and 2D-NMR and HRESIMS data, as well as chemical transformations. The effects of the compounds on human prostate cancer cells PC-3 and 22Rv1 were investigated.
Assuntos
Glucose/metabolismo , Poríferos/química , Antígeno Prostático Específico/metabolismo , Esteroides/química , Esteroides/farmacologia , Sulfatos/química , Sulfatos/farmacologia , Animais , Humanos , Espectroscopia de Ressonância Magnética/métodos , Células PC-3 , Esteróis/química , Esteróis/farmacologia , VietnãRESUMO
Spongian diterpenes are a group of marine natural compounds possessing various biological activities. However, their anticancer activity is still poorly studied and understood. We isolated six spongian diterpenes from the marine sponge Spongionella sp., including one new spongionellol A and five previously known molecules. The structures were elucidated using a detailed analysis MS and NMR spectra as well as by comparison with previously reported data. Two of them, namely, spongionellol A and 15,16-dideoxy-15α,17ß-dihydroxy-15,17-oxidospongian-16-carboxylate-15,17-diacetate exhibited high activity and selectivity in human prostate cancer cells, including cells resistant to hormonal therapy and docetaxel. The mechanism of action has been identified as caspase-dependent apoptosis. Remarkably, both compounds were able to suppress expression of androgen receptor (AR) and AR-splice variant 7, as well as AR-dependent signaling. The isolated diterpenes effectively inhibited drug efflux mediated by multidrug-resistance protein 1 (MDR1; p-glycoprotein). Of note, a synergistic effect of the compounds with docetaxel, a substrate of p-glycoprotein, suggests resensitization of p-glycoprotein overexpressing cells to standard chemotherapy. In conclusion, the isolated spongian diterpenes possess high activity and selectivity towards prostate cancer cells combined with the ability to inhibit one of the main drug-resistance mechanism. This makes them promising candidates for combinational anticancer therapy.