RESUMO
A chemical investigation of the tropical sponge Agelas sceptrum from Plana Cays (Bahamas) led to the isolation of two hybrid pyrrole-imidazole alkaloids (PIAs), 15'-oxoadenosceptrin (1) and decarboxyagelamadin C (2). Herein, we report their challenging structure elucidation established by NMR and ECD spectroscopy. 15'-Oxoadenosceptrin (1) shows sceptrin merged with an adenine moiety, not yet encountered in the PIA family, whereas decarboxyagelamadin C (2) is a close derivative of agelamadins C to E recently isolated from an Agelas sp. from Okinawa.
Assuntos
Agelas/química , Alcaloides/isolamento & purificação , Hidrocarbonetos Bromados/isolamento & purificação , Imidazóis/isolamento & purificação , Pirróis/isolamento & purificação , Alcaloides/química , Animais , Bahamas , Hidrocarbonetos Bromados/química , Imidazóis/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pirróis/químicaRESUMO
Nine new bromopyrrole alkaloids, aspidostomides A-H and aspidazide A (1-9), were isolated from the Patagonian bryozoan Aspidostoma giganteum. Aspidostomides A-H have dibromotyrosine- or bromotryptophan-derived moieties forming either linear amides or pyrroloketopiperazine-type lactams with a bromopyrrole carboxylic acid as a common structural motif. On the other hand, aspidazide A is a rare asymmetric acyl azide formed by an N-N link of two different pyrroloketopiperazine lactams and is the first isolated compound of this class from marine invertebrates. This work is the first report of secondary metabolites isolated from a bryozoan from the Patagonian region. The structures of compounds 1-9 were elucidated by spectroscopic methods and chemical transformations. One of these compounds, aspidostomide E (5), was moderately active against the 786-O renal carcinoma cell line.
Assuntos
Alcaloides/isolamento & purificação , Hidrocarbonetos Bromados/isolamento & purificação , Agelas/química , Alcaloides/química , Animais , Ácidos Carboxílicos , Humanos , Hidrocarbonetos Bromados/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pirróis/químicaRESUMO
Chemical analysis of the Chinese marine sponge Xestospongia testudinaria afforded a library of brominated polyunsaturated lipids including eight new compounds, named xestonarienes A-H (3-10) and thirteen known analogues (11-23). The structures of the new compounds were elucidated by detailed spectroscopic analysis and by comparison with literature data. The isolated lipids were evaluated for their inhibitory activity against pancreatic lipase (PL), an essential enzyme for efficient fat digestion and the major metabolite, 14, exhibited a marked inhibitory activity (IC50 = 3.11 µM), similar to that of the positive control Orlistat (IC50 = 0.78 µM). The preliminary structure-activity relationships on the series of compounds clearly evidenced that a terminal (E)-enyne functionality, a diyne within the chain, and methyl ester group are all key functional groups for the activity of this class of PL inhibitors. Further biological investigation on compound 14 revealed a significant decrease in the plasma triglyceride level following an oral lipid challenge in C57BLKS/J male mice. Acute toxicology study demonstrated that compound 14 was non-toxic up to 1600 mg/kg p.o in mice. This is the first report of the PL inhibitory activity for brominated polyunsaturated lipids and the obtained results qualify compound 14 as a potent and bioavailable drug candidate for a mild and safe treatment to prevent and reduce obesity.
Assuntos
Inibidores Enzimáticos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Hidrocarbonetos Bromados/farmacologia , Lipase/antagonistas & inibidores , Lipídeos/farmacologia , Xestospongia/química , Animais , China , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/isolamento & purificação , Feminino , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/isolamento & purificação , Lipase/metabolismo , Lipídeos/química , Lipídeos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Pâncreas/enzimologia , Relação Estrutura-Atividade , SuínosRESUMO
In the present study the occurrence of emerging hydrophobic organic pollutants in sediment samples from South America (Chile and Colombia) was investigated for the first time. Nineteen Chilean and thirteen Colombian sediment samples were analyzed in order to determine their content of brominated flame retardants (BFRs) (including PBDEs and emerging BFRs) as well as UV filters (UV-F). Samples were collected from neighboring aquatic ecosystems highly urbanized and industrialized in Colombia (Magdalena River area) and Chile (Biobio region). Different analytical procedures were applied depending on the selected analytes, based on chromatographic and mass spectrometric methodologies (GC-MS and LC-MS-MS). In general, concentration levels of both BFRs (up to 2.43 and 143ngg(-1) dw of PBDEs in Chile and Colombia, respectively) and UV-F (nd-2.96 and nd-54.4ngg(-1) dw in Chile and Colombia, respectively) were in the low range of published data, and the contribution of BFRs was higher than that of UV-F for almost all the sampled sediments.
Assuntos
Poluentes Ambientais/análise , Poluentes Ambientais/química , Sedimentos Geológicos/química , Interações Hidrofóbicas e Hidrofílicas , Compostos Orgânicos/análise , Compostos Orgânicos/química , Raios Ultravioleta , Chile , Colômbia , Retardadores de Chama/análise , Hidrocarbonetos Bromados/análise , Hidrocarbonetos Bromados/químicaRESUMO
In this study the nature of the bonding in a series of dimethylhalonium ylides (fluoronium, chloronium, bromonium and iodonium) was analyzed by means of topological methodologies (AIM and ELF analysis), to document the changes in the nature of the C-X bonds (X = F, Cl, Br, I) upon the series. For the sake of comparison the same study was performed on the corresponding dimethylhalonium cations (XC 2H 6 (+)) and the XCH 3 series. The wave functions used for the topological analysis were obtained at B3LYP level using extended triple-zeta basis sets. The formation of the cationic XC 2H 6 (+) structures can be interpreted to arise from the interaction between the XCH 3 and CH 3 (+) moieties. The resultant structures can be explained in terms of the superposition of two electrostatically interacting and two dative mesomeric structures. The halogen-carbon bonds have all the characteristics of the charge-shift (CS) bonds. The analysis of the C-X bond in the XC 2H 5 series shows a progressive reinforcing of the CH 3X-CH 2 bond, from FC 2H 5 that can be considered as formed from two fragments, FCH 3 and CH 2, to IC 2H 5, in which the CH 3I-CH 2 bond has all the features of a multiple bond involving atoms bearing lone pairs. Particularly interesting is BrC 2H 5, in which a special type of bond (hybrid covalent-dative double bond) has been characterized. The energetic stability of the XC 2H 5 structures with respect to the dissociation into the XCH 2 + CH 3 and XCH 3 + CH 2 ground-state fragments was studied in detail.
Assuntos
Carbono/química , Halogênios/química , Hidrocarbonetos Bromados/química , Hidrocarbonetos Clorados/química , Cátions , Simulação por Computador , Ligação de Hidrogênio , Modelos Moleculares , Estrutura MolecularRESUMO
The title compounds, C(12)H(9)ClO(4), (I), and C(12)H(9)BrO(4), (II), are isomorphous and crystallize in the monoclinic space group P2(1)/c. Both compounds present an anti conformation between the 3-carboxy and the lactone carbonyl groups. Both carbonyl groups are out of the plane defined by the remaining chromene atoms, by 8.37 (6) and 17.57 (6) degrees for (I), and by 9.07 (8) and 18.96 (18) degrees for (II), owing to their involvement in intermolecular interactions. In both compounds, layers of centrosymmetric hydrogen-bonded dimers are developed in the [-5 -2 22] plane through C-H...O interactions, involving both carbonyl groups as acceptors. Two families of dimers stack through C=O...C=O, C=O...pi and C-X...C=O (X = Cl and Br) dipolar interactions, as well as a C-H...pi interaction, developing the three-dimensional structure along the c axis.
Assuntos
Cumarínicos/química , Compostos Heterocíclicos com 2 Anéis/química , Hidrocarbonetos Bromados/química , Hidrocarbonetos Clorados/químicaRESUMO
Neuronal nicotinic acetylcholine receptors subserve predominantly modulatory roles in the brain, making them attractive therapeutic targets. Natural products provide key leads in the quest for nicotinic receptor subtype-selective compounds. Cytisine, found in Leguminosae spp., binds with high affinity to alpha4beta2* nicotinic receptors. We have compared the effect of C3 and C5 halogenation of cytisine and methylcytisine (MCy) on their interaction with native rat nicotinic receptors. 3-Bromocytisine (3-BrCy) and 3-iodocytisine (3-ICy) exhibited increased binding affinity (especially at alpha7 nicotinic receptors; Ki approximately 0.1 microM) and functional potency, whereas C5-halogenation was detrimental. 3-BrCy and 3-ICy were more potent than cytisine at evoking [3H]dopamine release from striatal slices (EC50 approximately 11 nM), [3H]noradrenaline release from hippocampal slices (EC50 approximately 250 nM), increases in intracellular Ca2+ in PC12 cells and inward currents in Xenopus oocytes expressing human alpha3beta4 nicotinic receptor (EC50 approximately 2 microM). These compounds were also more efficacious than cytisine. C3-halogenation of cytisine is proposed to stabilize the open conformation of the nicotinic receptor but does not enhance subtype selectivity.
Assuntos
Alcaloides/farmacologia , Hidrocarbonetos Bromados/farmacologia , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/metabolismo , Alcaloides/química , Alcaloides/metabolismo , Animais , Azocinas/química , Azocinas/metabolismo , Azocinas/farmacologia , Ligação Competitiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Cálcio/metabolismo , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Nicotina/antagonistas & inibidores , Nicotina/farmacologia , Agonistas Nicotínicos/química , Agonistas Nicotínicos/metabolismo , Norepinefrina/metabolismo , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Células PC12 , Quinolizinas/química , Quinolizinas/metabolismo , Quinolizinas/farmacologia , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Receptores Nicotínicos/genética , Receptores Nicotínicos/fisiologia , XenopusRESUMO
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).