RESUMO
Three decahydroisoquinoline alkaloids, lepadins I-K, were isolated from a specimen of Didemnum sp. collected in the Bahamas. The structures of the new compounds were assigned by an integrated analysis of MS, IR, and 1H, 13C, and 2D NMR spectra. Like previously reported lepadins, the structures of the new compounds contain a decahydroquinoline heterocyclic core in lepadin I, and a new variation, an octahydroquinoline in lepadin J, but differ from earlier reported compounds by acylation of the 3-hydroxyl group by a rare 3'-methylthioacrylate. The absolute configuration of lepadin I was solved by interpretation of NOE measurements, and exciton coupled circular dichroism (ECCD) of the corresponding N- p-bromobenzoyl derivative. The latter constitutes a general method for determination of absolute configuration of the entire lepadin family. The configuration of the remote side-chain secondary carbinol was solved by the modified Mosher's esters method. Lepadin I inhibited butyrylcholineesterase (BuChE, IC50 3.1 µM), but only weakly inhibited acetylcholineesterase (AChE) (10% at 100 µM).
Assuntos
Alcaloides/química , Isoquinolinas/química , Quinolinas/química , Urocordados/química , Animais , Bahamas , Modelos Moleculares , Estrutura MolecularRESUMO
The new pyrrole-imidazole and pyrrole-guanidine alkaloids 4-debromooroidin (1), 4-debromougibohlin (2), 5-debromougibohlin (3), and 5-bromopalau'amine (4), along with the known hymenidin (5) and (+)-monobromoisophakellin (6), have been isolated from a Dictyonella sp. marine sponge, collected at the Amazon River mouth. The bromine-substitution pattern observed for compounds 1, 2 and 4 is unusual among bromopyrrole alkaloids isolated from marine sponges. The 20S proteasome inhibitory activities of compounds 1-6 have been recorded, with 5-bromopalau'amine (4) being the most active in this series.
Assuntos
Poríferos/química , Inibidores de Proteassoma/química , Inibidores de Proteassoma/farmacologia , Pirróis/química , Pirróis/farmacologia , Animais , Brasil , Estrutura Molecular , Complexo de Endopeptidases do Proteassoma , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genéticaRESUMO
A new cyclic peptide, jamaicensamide A, composed of six amino acids, including a thiazole-homologated amino acid, was isolated from the Bahamian sponge Plakina jamaicensis, along with known compounds bitungolide A and franklinolide A. The structure of the title peptide was solved by integrated analysis of MS, 1D and 2D NMR data, oxidation-hydrolyses to α-amino acids, and their stereodetermination by Marfey's method. The close structural resemblance of Western Atlantic-derived jamaicensamide A to known Western Pacific-derived peptides of lithistid sponges in the genus Theonella and Discodermia suggests a common origin: the symbiotic bacterium Entotheonella sp., a so-called "talented producer" responsible for biosynthesis of most Theonella-associated peptides. Similar natural products from sponges of disparate genera evince the likelihood that these invertebrates harbor the same or a very similar symbiont.
Assuntos
Produtos Biológicos/isolamento & purificação , Peptídeos Cíclicos/isolamento & purificação , Theonella/química , Tiazóis/química , Aminoácidos/química , Animais , Bahamas , Produtos Biológicos/química , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/químicaRESUMO
Cryptococcus gattii is a human pathogen and causative agent of a pernicious, sometimes fatal, disseminated fungal disease. Investigation of antifungal extracts of the marine sponge association Plakortis halichondrioides-Xestospongia deweerdtae and the sponge Plakortis zyggompha from the Bahamas led to the discovery and isolation of 6-epi-7,8-dihydroplakortide K (1), plakortide AA (2), and three new plakinic acids, N-P (4-6; unstable 1,2-dioxolanes bearing benzyl-substituted conjugated dienes), along with known plakinic acids L, K, and M.5 Chiroptical comparisons and DFT calculations of (13)C NMR chemical shifts were used to assign the absolute stereostructure of 4. The stereospecific base-promoted rearrangement-saponification of 1 to 10 was briefly investigated and showed tight kinetic control and stereospecific formation of the new C-2 stereocenter with inversion at C-3. Plakinic acid M and plakortides 9 and 11 exhibited antifungal activity against C. gattii (MIC90 = 2.4 to 36 µM), but plakinic acids N-P were inactive under the same conditions.
Assuntos
Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Cryptococcus gattii/química , Peróxidos/isolamento & purificação , Peróxidos/farmacologia , Plakortis/microbiologia , Xestospongia/microbiologia , Animais , Antifúngicos/química , Bahamas , Produtos Biológicos/química , Dioxanos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Biologia Marinha , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peróxidos/química , Relação Estrutura-AtividadeRESUMO
Investigation of antifungal natural products from the marine sponge Pseudaxinella reticulata from the Bahamas led to the discovery of new crambescin homologues (1, 2) and enantiomers (3, 4) of known natural products. The cyclic-guanidine structures were solved through analysis of 2D NMR, MS-MS, and CD data. The absolute configurations of 1-4 were established as 13R-opposite of known homologues reported from Crambe crambe obtained from the Mediterranean Sea-by comparison of their CD spectra with predicted Cotton effects obtained from DFT calculations. Antifungal activities of 1-4 against the pathogenic strains Candida albicans and Cryptococcus sp. were observed to correlate potency (MIC50 and MIC90) with the length of the alkyl side chain.
Assuntos
Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Guanidinas/isolamento & purificação , Guanidinas/farmacologia , Compostos Heterocíclicos com 2 Anéis/isolamento & purificação , Compostos Heterocíclicos com 2 Anéis/farmacologia , Poríferos/química , Animais , Antifúngicos/química , Bahamas , Produtos Biológicos/química , Candida albicans/efeitos dos fármacos , Cryptococcus/efeitos dos fármacos , Guanidinas/química , Compostos Heterocíclicos com 2 Anéis/química , Biologia Marinha , Mar Mediterrâneo , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: Marine sponges are among the most promising sources of chemically diversified fatty acids (FAs). In addition, several studies have shown the effect of polyunsaturated FAs on cancer therapy. This research carried out a biological and chemical evaluation of the sponge Scopalina ruetzleri collected on the South Brazilian coastline. METHODS: Bioassay-guided fractionation of S. ruetzleri was performed in human glioma (U87) and neuroblastoma (SH-SY5Y) cell lines, and the in-vitro effects on free radicals were evaluated. KEY FINDINGS: The ethyl acetate fraction of S. ruetzleri showed promising cytotoxic effects in cancer cell lines, with IC50 < 20 µg/ml. Fingerprint (1) H Nuclear Magnetic Resonance (NMR) analysis showed that this fraction is mainly constituted of FAs. Through FA methyl ester analysis, it was possible to identify 32 FAs. In addition, some minor unusual FAs for the marine biosphere were identified. The results of conjugated dienes method showed that FAs fraction, at concentrations above 50 µg/ml, has a pro-oxidant effect, indicating that lipid peroxidation may be partially responsible for the mechanism of cytotoxicity on cancer cells. CONCLUSION: This work also contributes to studies that focus on the application of FAs on cancer therapy as a new adjuvant to radio or chemotherapy, or as a chemotherapeutic agent.
Assuntos
Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos/farmacologia , Poríferos/química , Animais , Antineoplásicos/química , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Ácidos Graxos/química , Ácidos Graxos/toxicidade , HumanosRESUMO
Salvadenosine, (1) a rare 5'-deoxy-5'-(methylthio) nucleoside, was isolated from the deep-water Bahaman tunicate Didemnum sp. The structure was solved by integrated analysis of MS and 1D and 2D NMR data. We revise the structure of the known natural product, hamiguanosinol, which is a constitutional isomer of 1, to 5 by interpretation of the spectroscopic data and comparison with synthesized nucleosides.
Assuntos
Nucleosídeos/química , Tionucleosídeos/química , Urocordados/química , Animais , Bahamas , Região do Caribe , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Tionucleosídeos/isolamento & purificaçãoRESUMO
Halisphingosines A (1) and B (2), modified long-chain sphingoid bases, from the marine sponge Haliclona tubifera collected in Brazil, were characterized after conversion to their N-Boc derivatives. The 2R,3R,6R configuration of halisphingosine A, a compound first reported from Haliclona sp. from South Korea, was confirmed using a novel CD approach: deconvolution of exciton coupling from mono- and trinaphthoyl derivatives obtained by derivatization of the natural product. The sensitive CD deconvolution method, applicable to submilligram samples, simultaneously predicted the relative and absolute configuration of three stereocenters in halisphingosine A with precision and accuracy. Halisphingosine B was assigned by correlation to halisphingosine A.
Assuntos
Haliclona/química , Esfingolipídeos/isolamento & purificação , Animais , Brasil , Dicroísmo Circular , Biologia Marinha , Estrutura Molecular , República da Coreia , Esfingolipídeos/química , EstereoisomerismoRESUMO
The absolute stereostructures of the components of symplocin A (3), a new N,N-dimethyl-terminated peptide from the Bahamian cyanobacterium Symploca sp., were assigned from spectroscopic analysis, including MS, 2D NMR, and Marfey's analysis. The complete absolute configuration of symplocin A, including the unexpected D-configurations of the terminal N,N-dimethylisoleucine and valic acid residues, was assigned by chiral-phase HPLC of the corresponding 2-naphthacyl esters, a highly sensitive, complementary strategy for assignment of N-blocked peptide residues where Marfey's method is ineffectual or other methods fall short. Symplocin A exhibited potent activity as an inhibitor of cathepsin E (IC(50) 300 pM).
Assuntos
Catepsina E/antagonistas & inibidores , Cianobactérias/química , Naftalenos/química , Peptídeos/isolamento & purificação , Bahamas , Cromatografia Líquida de Alta Pressão , Ésteres , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos/química , Peptídeos/farmacologiaRESUMO
The complete stereostructures of xestoproxamines A-C, from the Bahamian sponge Neopetrosia proxima, were assigned from spectroscopic analysis, including MS, 2D NMR, and integrated degradation-CD analysis. Two new CD application protocols are described for defining absolute configuration: one for allylic methyl groups in branched chains and a second for the heterocyclic core bis-piperidine with specific applicability to other members of this class alkaloids--known for their stereoheterogeneity--and tertiary cyclic amines in general.
Assuntos
Alcaloides/química , Alcaloides/isolamento & purificação , Piperidinas/química , Piperidinas/isolamento & purificação , Poríferos/química , Aminas/química , Aminas/isolamento & purificação , Animais , Bahamas , Dicroísmo Circular , Modelos Moleculares , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Long-chain polyacetylene alcohols, faulknerynes A-C, along with known compounds diplynes A, C and E, were isolated from two specimens of the encrusting sponge, Diplastrella sp., collected from the surface of coral in the Bahamas. Two CD methods were critically evaluated for their suitability to terminal propargylic glycols and applied to assignment of configurations of faulkneryne A and diplyne C.
Assuntos
Pargilina/química , Poli-Inos/química , Poríferos/química , Animais , Antozoários/química , Bahamas , Dicroísmo Circular/métodos , Espectroscopia de Ressonância de Spin Eletrônica , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Poli-Inos/isolamento & purificaçãoRESUMO
The absolute configurations of fistularin-3, 11-epi-fistularin-3, and a related bis-oxazolidinone were determined by microscale hydrolysis followed by derivatization with 1-fluoro-2,4-dinitrophenyl-5-l-alaninamide. Samples of fistularin-3 from Verongid marine sponges collected in the Great Barrier Reef (Australia), Baía de Todos os Santos (Brazil), and the Key Largo, Florida (USA) varied in configuration at C11, a phenomenon that may be attributed to the involvement of stereochemically promiscuous hydroxylase enzymes. Variability in C11 configuration in fistularin-3 samples may have been overlooked in previously reported encounters due to the similarity of spectroscopic properties of fistularin-3 and 11-epi-fistularin-3 and their coelution under chromatographic conditions. Stereochemical heterogeneity at C11 in fistularin-3 samples suggests a possibility of a native biotransformation of suitable precursor in Verongid sponges by their associated microbial flora.
Assuntos
Alanina/análogos & derivados , Isoxazóis/química , Poríferos/química , Tirosina/análogos & derivados , Tirosina/química , Animais , Austrália , Brasil , Dinitrobenzenos , Florida , Isoxazóis/análise , Oxigenases de Função Mista/metabolismo , Estrutura Molecular , Poríferos/enzimologia , Poríferos/metabolismo , Estereoisomerismo , Tirosina/análiseRESUMO
The novel antifungal compound majusculoic acid was isolated from a cyanobacterial mat microbial community. The structure of majusculoic acid was solved by interpretation of mass spectrometric and NMR data and conversion to the corresponding methyl ester. Majusculoic acid exhibits antifungal activity against Candida albicans ATCC 14503 (MIC 8 microM).
Assuntos
Antifúngicos/isolamento & purificação , Candida albicans/efeitos dos fármacos , Cianobactérias/química , Ácidos Graxos Insaturados/isolamento & purificação , Hidrocarbonetos Bromados/isolamento & purificação , Antifúngicos/química , Antifúngicos/farmacologia , Bahamas , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
A new antifungal agent, (2S,3R)-2-aminododecan-3-ol (1), has been isolated from the ascidian Clavelina oblonga collected in Brazil. The structure of 1 was established by analysis of spectroscopic data, including absolute stereochemistry determined by circular dichroism analysis of the dibenzoyl derivative 2. Compound 1 displayed antifungal activity against Candida albicans ATCC 10231 with a MIC of 0.7 mug/mL and against Candida glabrata with a MIC of 30 microg/mL.
Assuntos
Antifúngicos/isolamento & purificação , Candida/efeitos dos fármacos , Dodecanol/análogos & derivados , Dodecanol/isolamento & purificação , Urocordados/química , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Brasil , Dicroísmo Circular , Dodecanol/química , Dodecanol/farmacologia , Estrutura Molecular , EstereoisomerismoRESUMO
[structure: see text]. A new 36-membered macrolactone, (25S,27S,29S,33S)-caylobolide A, was isolated from the Bahamian cyanobacterium Lyngbya majuscula. The structure of caylobolide contains an unprecedented repeated unit-a contiguous pentad of 1,5 diols-and a 1,3,5-triol. The relative steroechemistry of the 1,3,5-triol was determined using Kishi's Universal NMR database, and absolute stereochemistry at C25,27,29 and C33 were determined by Mosher's analysis. Caylobolide A exhibited in vitro cytotoxicity against human colon tumor cells (IC50 HCT 116, 9.9 microM).