RESUMO
Investigation of the Vietnamese marine sponge Rhabdastrella globostellata led to the isolation of two new polar isomalabaricanes: rhabdastrellosides A (1) and B (2). Their structures and stereochemistry were elucidated with the application of 1D and 2D NMR, HRESIMS, and HRESIMS/MS methods, as well as chemical modifications and GC-MS analysis. Metabolites 1 and 2 are the first isomalabaricanes with non-oxidized cyclopentane ring in the tricyclic core system. Moreover, having a 3-O-disaccharide moiety in their structures, they increase a very rare group of isomalabaricane glycosides. We report here a weak cytotoxicity of 1 and 2 toward human neuroblastoma SH-SY5Y cells and normal rat H9c2 cardiomyocytes, as well as the cytoprotective activity of rhabdastrelloside B (2) at 1 µM evaluated using CoCl2-treated SH-SY5Y and H9c2 cells.
Assuntos
Antineoplásicos , Neuroblastoma , Poríferos , Triterpenos , Animais , Humanos , Ratos , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Ensaios de Seleção de Medicamentos Antitumorais , Triterpenos/química , Poríferos/química , Antineoplásicos/químicaRESUMO
In continuation of our studies on a Vietnamese collection of a Stelletta sp., sponge we have isolated two new isomalabaricane triterpenoids, stellettins Q and R (1 and 2), and four new isomalabaricane-derived nor-terpenoids, stellettins S-V 3-6, along with previously known globostelletin N. Among them, compound 3 contains an acetylenic fragment, unprecedented in the isomalabaricane family and extremely rare in other marine sponge terpenoids. The structures and absolute configurations of all new compounds were established by extensive NMR, MS, and ECD analyses together with quantum-chemical modeling. Additionally, according to obtained new data we report the correction in stereochemistry of two asymmetric centers in the structures of two known isomalabaricanes, 15R,23S for globostelletin M and 15S,23R for globostelletin N.
Assuntos
Poríferos/química , Poríferos/metabolismo , Terpenos/química , Triterpenos/química , Alcinos/química , AnimaisRESUMO
The results of an investigation of the protective effects of five lanostane triterpenoids: 3ß-acetoxy-7ß,8ß-epoxy-5α-lanost-24-en-30,9α-olide (1), 3ß-hydroxy-7ß,8ß-epoxy-5α-lanost-24-en- 30,9α-olide (2), 29-nor-penasterone (3), penasterone (4), and acetylpenasterol (5), from a marine sponge, Penares sp., against paraquat-induced neuroblastoma Neuro-2a cell damage, are described. The influence of all compounds on viability of the Neuro-2a cells treated with paraquat (PQ) was studied with MTT and fluorescein diacetate assays as well as propidium iodide straining. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of the compounds as well as their influence on reactive oxygen species (ROS) level and mitochondrial membrane potential in PQ-treated neuronal cells were analyzed. Finally, the effect of the compounds on intracellular level of heat shock protein 70 kDa (Hsp70) and neurite outgrowth in PQ-treated Neuro-2a cells were studied. Studied triterpenoids demonstrated protective effects against PQ-induced neurotoxicity associated with the ability to reduce ROS intracellular level and diminish mitochondrial dysfunction. Acetylpenasterol (5), as a more promising neuroprotective compound, significantly increased the viability of Neuro-2a cells incubated with PQ as well as decreased intracellular ROS level in these cells. Moreover, acetylpenasterol induced Hsp70 expression in PQ-treated cells. It was also shown to inhibit PQ-induced neurite loss and recovered the number of neurite-bearing cells. The relationship between neuroprotective activity of the investigated compounds 1-5 and their chemical structure was also discussed.
Assuntos
Metaboloma , Neurotoxinas/toxicidade , Paraquat/toxicidade , Poríferos/química , Triterpenos/metabolismo , Animais , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Metaboloma/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Crescimento Neuronal/efeitos dos fármacos , Picratos/química , Espécies Reativas de Oxigênio/metabolismo , Triterpenos/químicaRESUMO
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
Four new oxysterols 1â»4 along with previously known oxygenated sterols 5â»14 were isolated from the sponge Inflatella sp., collected from the Sea of Okhotsk. Structures of 1â»4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses as well as by comparison of the corresponding experimental data with those reported in literature. The influence of compounds 1â»14 on the viability of neuronal Neuro2a cells treated by 6-hydroxydopamine and reactive oxygen species (ROS) formation in these cells was investigated.
Assuntos
Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Oxisteróis/química , Oxisteróis/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Poríferos/química , Animais , Antiparkinsonianos/química , Antiparkinsonianos/isolamento & purificação , Antiparkinsonianos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Oxidopamina , Oxisteróis/isolamento & purificação , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Six new triterpenoids (1-6) and the previously known penasterone, acetylpenasterol, and ergosta-4,24(28)-dien-3-one were isolated from a Penares sp. sponge collected from Vietnamese waters. Structures of the obtained compounds were established by extensive 1D and 2D NMR spectroscopy and mass spectrometry. Configurations of the triterpene epoxy lactones (1-4) were determined on the basis of NOESY and CD data and calculation of spin coupling constants and confirmed by X-ray crystallographic analysis of compound 2. The isolated triterpenoid 6 was cytotoxic against human leukemia HL-60 cells (IC50 = 9.7 µM).
Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Poríferos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Animais , Antineoplásicos/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Lanosterol/análogos & derivados , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Triterpenos/química , VietnãRESUMO
The first representatives of a new group of manzamine-related alkaloids with a previously unknown skeletal systems, namely, lissodendoric acids A (1) and B (2), were isolated from the sponge Lissodendoryx florida collected from the Sea of Okhotsk. The structures and absolute configurations have been elucidated by extensive spectroscopic analysis together with chemical transformations and quantum-chemical modeling. The lissodendoric acids show a potent capability to decrease the production of reactive oxygen species in neuroblastoma Neuro 2a and somewhat increase the survival of these cells upon treatment with 6-hydroxydopamine (an in vitro antiparkinson biotest).
Assuntos
Alcaloides/química , Animais , Estrutura Molecular , PoríferosRESUMO
Two new guaiane derivatives (1 and 2) along with six known sesquiterpenoids (3-8) were isolated from the gorgonian Menella woodin. Their structures -were elucidated by ID and 2D NMR and HRESIMS data as well as by comparison of their spectra with those in the literature. Relative configurations of asymmetric centers in 1 and 2 were suggested on the basis of NOESY and ID NOE correlations, absolute stereochemistry of these compounds was proposed in result of comparison of calculated (for both enatiomers) and experimental ECD. Some suggestions were made regarding a biosynthesis of guaiane sesquiterpenoids in this species. All the compounds were firstly isolated from M woodin.
Assuntos
Antozoários/química , Sesquiterpenos/química , Animais , Estrutura MolecularRESUMO
Eight new oxidized lanostane and nor-lanostane derivatives (1-8) along with the previously known penasterol (9) and 24-ethylcholesta-4,24(28)-dien-3-one (10) were isolated from a sponge Penares sp. collected from the Vietnamese waters. Structures of these minor compounds were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses and by comparison with earlier reported spectroscopic data. A hypothetic scheme of metabolism of the lanostane derivatives in sponges belonging to Penares and Erylus genera was proposed and discussed.
Assuntos
Poríferos/química , Triterpenos/química , Triterpenos/isolamento & purificação , Água , Animais , Etanol/química , VietnãRESUMO
Four new polyoxygenated sterol derivatives (1-4) along with the compounds (5-7) previously known from other biological sources were isolated from the gorgonian Menella woodin, collected from the Vietnamese waters. Structures of 1-4 were elucidated by the detailed NMR spectroscopic and mass-spectrometric analyses as well as comparison with those reported in literature data. Compounds 1, 4, and 6 decrease the production of reactive oxygen species (ROS) by the murine macrophages of RAW 264.7 line at induction by endotoxic lipopolysaccharide (LPS) from Escherichia coli.
Assuntos
Antozoários/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Esteroides/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Conformação Molecular , Espécies Reativas de Oxigênio/antagonistas & inibidores , Esteroides/química , Esteroides/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Chemical compositions of three collections of the red alga Laurencia nipponica from the western part of the Sea of Japan were studied. One of them contained a series of the previously known sesquiterpenoids. Another one gave C15 bromoallene ethers, predominantly. Finally, two new halogenated diterpenes, 15-bromoparguer-9(11)-ene-16-ol and 15-bromoparguer-7-ene-16-ol, were isolated from the third collection of the same species. Structures of these diterpenoids were established by 1D and 2D NMR (1H-1H COSY, DEPT, HMQC, HMBC and NOESY) along with molecular calculations for conformations having lowest energies and mass spectroscopy. Diversity and variability of halogenated secondary metabolites in L. nipponica were discussed.