RESUMO
Low molecular weight secondary metabolites of marine fungi Aspergillus flocculosus, Aspergillus terreus and Penicillium sp. from Van Phong and Nha Trang Bays (Vietnam) were studied and a number of polyketides, bis-indole quinones and terpenoids were isolated. The structures of the isolated compounds were determined by 1D and 2D NMR and HR-ESI-MS techniques. Stereochemistry of some compounds was established based on ECD data. A chemical structure of asterriquinone F (6) was thoroughly described for the first time. Anthraquinone (13) was firstly obtained from a natural source. Neuroprotective influences of the isolated compounds against 6-OHDA, paraquat and rotenone toxicity were investigated. 4-Hydroxyscytalone (1), 4-hydroxy-6-dehydroxyscytalone (2) and demethylcitreoviranol (3) have shown significant increasing of paraquat- and rotenone-treated Neuro-2a cell viability and anti-ROS activity.
Assuntos
Antiparkinsonianos/farmacologia , Aspergillus/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Penicillium/metabolismo , Animais , Antiparkinsonianos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Estrutura Molecular , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Paraquat/toxicidade , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Espécies Reativas de Oxigênio/metabolismo , Rotenona/toxicidade , Metabolismo Secundário , Relação Estrutura-Atividade , VietnãRESUMO
Two new auroglaucin-derived compounds, niveoglaucins A (1) and B (2), together with four known related compounds were isolated from extract of the marine sediment-derived strain of Aspergillus niveoglaucus. The structures of these compounds were determined by 1D and 2D NMR spectroscopy and high resolution MS. The plausible biosynthetic pathway was proposed for new compounds 1 and 2. The neuroprotective activity in 6-OHDA-induced Parkinson's disease cell model was shown for niveoglaucin A (1).
Assuntos
Aspergillus/química , Sedimentos Geológicos/química , Fármacos Neuroprotetores/isolamento & purificação , Animais , Antiparkinsonianos/isolamento & purificação , Linhagem Celular , Fungos/química , Sedimentos Geológicos/microbiologia , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Modelos Biológicos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Oxidopamina/efeitos adversos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/patologia , VietnãRESUMO
Four new diketopiperazine alkaloids, citriperazines A-D were isolated from algae-derived Penicillium sp. KMM 4672. The structures of compounds 1-4 were determined using spectroscopic methods. The absolute configurations of compounds 1 and 4 were established by comparison of calculated and experimental ECD spectra. The cytotoxicity of compounds 1-4 against several human prostate cell lines was evaluated.
Assuntos
Dicetopiperazinas/isolamento & purificação , Penicillium/química , Alcaloides/química , Alcaloides/isolamento & purificação , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Dicetopiperazinas/química , Humanos , Conformação Molecular , Estrutura Molecular , Análise EspectralRESUMO
Seven known echinulin-related indolediketopiperazine alkaloids (1-7) were isolated from the Vietnamese sediment-derived fungus Aspergillus niveoglaucus. Using chiral HPLC, the enantiomers of cryptoechinuline B (1) were isolated as individual compounds for the first time. (+)-Cryptoechinuline B (1a) exhibited neuroprotective activity in 6-OHDA-, paraquat-, and rotenone-induced in vitro models of Parkinson's disease. (-)-Cryptoechinuline B (1b) and neoechinulin C (5) protected the neuronal cells against paraquat-induced damage in a Parkinson's disease model. Neoechinulin B (4) exhibited cytoprotective activity in a rotenone-induced model, and neoechinulin (7) showed activity in the 6-OHDA-induced model.
Assuntos
Alcaloides/farmacologia , Aspergillus/química , Fármacos Neuroprotetores/farmacologia , Piperazina/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Sedimentos Geológicos/química , Sedimentos Geológicos/microbiologia , Humanos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Paraquat/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/tratamento farmacológico , Piperazina/análogos & derivados , Piperazina/química , Piperazina/isolamento & purificaçãoRESUMO
Four new compounds were isolated from the Vietnamese marine sediment-derived fungus Aspergillus flocculosus, one aspyrone-related polyketide aspilactonol G (2), one meroterpenoid 12-epi-aspertetranone D (4), two drimane derivatives (7,9), together with five known metabolites (1,3,5,6,8,10). The structures of compounds 1-10 were established by NMR and MS techniques. The absolute stereoconfigurations of compounds 1 and 2 were determined by a modified Mosher's method. The absolute configurations of compounds 4 and 7 were established by a combination of analysis of ROESY data and coupling constants as well as biogenetic considerations. Compounds 7 and 8 exhibited cytotoxic activity toward human prostate cancer 22Rv1, human breast cancer MCF-7, and murine neuroblastoma Neuro-2a cells.
Assuntos
Antineoplásicos/farmacologia , Organismos Aquáticos/metabolismo , Aspergillus/metabolismo , Produtos Biológicos/farmacologia , Fungos/metabolismo , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Sedimentos Geológicos/microbiologia , Humanos , Células MCF-7 , Espectroscopia de Ressonância Magnética/métodos , Biologia Marinha/métodos , Camundongos , Sesquiterpenos Policíclicos/farmacologia , Policetídeos/farmacologia , Sesquiterpenos/farmacologiaRESUMO
A new melatonin analogue 6-hydroxy-N-acetyl-ß-oxotryptamine (1) was isolated from the marine-derived fungus Penicillium sp. KMM 4672. It is the second case of melatonin-related compounds isolation from microfilamentous fungi. The neuroprotective activities of this metabolite, as well as 3-methylorsellinic acid (2) and 8-methoxy-3,5-dimethylisochroman-6-ol (3) from Penicillium sp. KMM 4672, candidusin A (4) and 4â³-dehydroxycandidusin A (5) from Aspergillus sp. KMM 4676, and diketopiperazine mactanamide (6) from Aspergillus flocculosus, were investigated in the 6-hydroxydopamine (6-OHDA)- and paraquat (PQ)-induced Parkinson's disease (PD) cell models. All of them protected Neuro2a cells against the damaging influence of 6-OHDA to varying degrees. This effect may be realized via a reactive oxygen species (ROS) scavenging pathway. The new melatonin analogue more effectively protected Neuro2A cells against the 6-OHDA-induced neuronal death, in comparison with melatonin, as well as against the PQ-induced neurotoxicity. Dehydroxylation at C-3â³ and C-4â³ significantly increased free radical scavenging and neuroprotective activity of candidusin-related p-terphenyl polyketides in both the 6-OHDA- and PQ-induced PD models.
Assuntos
Organismos Aquáticos/microbiologia , Aspergillus/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Penicillium/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antiparkinsonianos/química , Antiparkinsonianos/isolamento & purificação , Antiparkinsonianos/farmacologia , Aspergillus/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Melatonina/análogos & derivados , Camundongos , Fármacos Neuroprotetores/isolamento & purificação , Oxidopamina , Paraquat , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Penicillium/isolamento & purificação , Policetídeos/química , Policetídeos/isolamento & purificação , Policetídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Four new indole-diterpene alkaloids asperindoles Aâ»D (1â»4) and the known p-terphenyl derivative 3″-hydroxyterphenyllin (5) were isolated from the marine-derived strain of the fungus Aspergillus sp., associated with an unidentified colonial ascidian. The structures of 1â»5 were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of 1â»4 were determined by the combination of ROESY data, coupling constants analysis, and biogenetic considerations. Asperindoles C and D contain a 2-hydroxyisobutyric acid (2-HIBA) residue, rarely found in natural compounds. Asperindole A exhibits cytotoxic activity against hormone therapy-resistant PC-3 and 22Rv1, as well as hormone therapy-sensitive human prostate cancer cells, and induces apoptosis in these cells at low-micromolar concentrations.
Assuntos
Antineoplásicos/farmacologia , Aspergillus/química , Diterpenos/farmacologia , Alcaloides Indólicos/farmacologia , Urocordados/microbiologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Organismos Aquáticos/microbiologia , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Docetaxel , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Estrutura Molecular , Estereoisomerismo , Taxoides/farmacologiaAssuntos
Antineoplásicos/farmacologia , Beauveria/metabolismo , Sedimentos Geológicos/microbiologia , Policetídeos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Beauveria/isolamento & purificação , Humanos , Masculino , Policetídeos/química , Policetídeos/isolamento & purificação , Metabolismo SecundárioRESUMO
Three new epidithiodiketopiperazines pretrichodermamides D-F (1-3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide С (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures of compounds 1-5 were determined based on spectroscopic methods. The absolute configuration of pretrichodermamide D (1) was established by a combination of modified Mosher's method, NOESY data, and biogenetic considerations. N-Methylpretrichodermamide B (5) showed strong cytotoxicity against 22Rv1 human prostate cancer cells resistant to androgen receptor targeted therapies.
Assuntos
Produtos Biológicos/química , Diterpenos/química , Fungos/química , Penicillium/química , Piperazinas/química , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Biologia Marinha/métodos , Estrutura Molecular , Piperazinas/farmacologiaRESUMO
N-Methylpretrichodermamide B (I), pretrichodermamide C (H), quinolactacide (III) and 8-methoxy-3,5-dimethyl-3,4-dihydro-IH-isochromen-6-ol (IV), isolated from the marine fungus Penicillium sp., were examined for their ability to stimulate growth of seedling roots of buckwheat (Fagopyrum esculentum Moench), wheat (Triticum aestivum L.), soy {Glycine max (L.) Merr.}, and barley (Hordeum vulgare), It was shown that the stimulatory effects depend on the chemical structure of the compounds and on the plant species. Compounds I and III improved the rate of growth of seedling roots of buckwheat (1) and wheat (2), compound II stimulated growth of buckwheat roots (1), and compound IV improved growth of seedling roots of wheat (2) and soy (3). These compounds can be recommended for field study as plant growth stimulators.
Assuntos
Penicillium/química , Raízes de Plantas/efeitos dos fármacos , Plântula/efeitos dos fármacos , Organismos Aquáticos/química , Fagopyrum , Hordeum , Estrutura Molecular , Raízes de Plantas/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Glycine max , Triticum , VietnãRESUMO
A new polyketide 1 and a new decaline derivative 2 were isolated from a sediment-derived fungus Aspergillus carneus Blochwitz, together with one known bisabolane sesquiterpenoid and seven known polyketide metabolites. The structures of the isolated compounds were established by HR-MS, and 1D and 2D NMR spectroscopy. The cytotoxic and antiradical activities of the isolated compounds were evaluated.
Assuntos
Aspergillus/química , Policetídeos/isolamento & purificação , Animais , Aspergillus/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Sedimentos Geológicos/microbiologia , Camundongos , Estrutura Molecular , Policetídeos/químicaRESUMO
Oxirapentyn A (1), oxirapentyn B (2), and oxirapentyn E (3) were examined for their ability to stimulate growth of seedling roots of barley (Hordeum vulgare L.), buckwheat (Fagopyrum esculentum Moench), corn (Zea mays L.), soy {Glycine max (L.) Merr.}, and wheat (Triticum aestivum L.). It was shown that the stimulatory effects depend on the chemical structure of the oxirapentyns and on the plant species. Compounds 1, and 2 are efficient for growth of seedling roots of barley, and wheat, whereas compound 3, at different concentrations, stimulates growth of seedling roots of maize, soy, and wheat. These compounds can be recommended for field study as plant growth stimulators.
Assuntos
Ascomicetos/química , Benzopiranos/química , Germinação/efeitos dos fármacos , Plantas/efeitos dos fármacos , Sementes/efeitos dos fármacos , Benzopiranos/farmacologia , Estrutura MolecularRESUMO
Six new highly oxygenated chromene derivatives, oxirapentyns F-K (2-7), one new polyketide (8), one new benzofurane (9), and two known cyclodepsipeptides, isoisariin B and isaridin E, were isolated from the lipophilic extract of the marine-derived fungus Isaria felina KMM 4639. The structures of compounds 2-9 were determined using spectroscopic methods. The relative configurations of compounds 2-7 were established through a combination of NOE data and spin coupling constants, and these results were confirmed by X-ray crystallographic analysis of 4. The absolute structures of all oxirapentyns were assumed based on their biogenetic relationship and confirmed using the modified Mosher's method on 2 and 7. Isariketide (8) showed moderate cytotoxicity toward HL-60 cells.
Assuntos
Alcinos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Benzopiranos/isolamento & purificação , Depsipeptídeos/isolamento & purificação , Sedimentos Geológicos/química , Hypocreales/química , Alcinos/química , Alcinos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Depsipeptídeos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Biologia Marinha , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oceanos e MaresRESUMO
A new decaline derivative, decumbenone C (1) along with four known compounds, decumbenones A (2) and B (3), diorcinol (4), and brevianamide F (5) were isolated from the marine fungus Aspergillus sulphureus KMM 4640. Decumbenone C shows potent cytotoxic activity against SK-MEL-5 human melanoma cells with IC(50) values of 0.9 µM.
Assuntos
Antineoplásicos/isolamento & purificação , Aspergillus/química , Sedimentos Geológicos , Naftalenos/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Antineoplásicos/farmacologia , Aspergillus/isolamento & purificação , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sedimentos Geológicos/microbiologia , Humanos , Concentração Inibidora 50 , Cetonas/isolamento & purificação , Cetonas/farmacologia , Estrutura Molecular , Naftalenos/farmacologia , Sesquiterpenos/farmacologiaRESUMO
Three new indole alkaloids, shearinines D, E, and F (1-3), together with the known shearinine A (4) were isolated from the marine-derived strain of the fungus Penicillium janthinellum Biourge. The chemical structures of 1-4 were established by 2D NMR and HREIMS data. Shearinines A, D, and E induce apoptosis in human leukemia HL-60 cells, and shearinine E also inhibits EGF-induced malignant transformation of JB6 P+ Cl 41 cells in a soft agar.
Assuntos
Anticarcinógenos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Penicillium/química , Anticarcinógenos/química , Anticarcinógenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Biologia Marinha , Estrutura MolecularRESUMO
The marine strain Pseudoalteromonas maricaloris KMM 636T was found to produce an inseparable mixture of two brominated yellow main pigments, bromoalterochromide A and A', in a ratio of 3: 1. Both pigments are Thr-Val-Asn-Asn-X pentapeptide lactones, where the amino group of Thr is acylated with 9-(3-bromo-4-hydroxyphenyl)-nona-2,4,6,8-tetraenoic acid, and X is aIle and Leu, respectively. They possess cytotoxic effects on developing eggs of the sea urchin Strongylocentrotus intermedius, but no antibiotic activity.