RESUMO
The metabolic profile of the Aspergillus sp. 1901NT-1.2.2 sponge-associated fungal strain was investigated using the HPLC MS technique, and more than 23 peaks in the HPLC MS chromatogram were detected. Only two minor peaks were identified as endocrocin and terpene derivative MS data from the GNPS database. The main compound was isolated and identified as known anthraquinone derivative vismione E. The absolute stereochemistry of vismione E was established for the first time using ECD and quantum chemical methods. Vismione E showed high cytotoxic activity against human breast cancer MCF-7 cells, with an IC50 of 9.0 µM, in comparison with low toxicity for normal human breast MCF-10A cells, with an IC50 of 65.3 µM. It was found that vismione E inhibits MCF-7 cell proliferation and arrests the cell cycle in the G1 phase. Moreover, the negative influence of vismione E on MCF-7 cell migration was detected. Molecular docking of vismione E suggested the IMPDH2 enzyme as one of the molecular targets for this anthraquinone derivative.
Assuntos
Antineoplásicos , Poríferos , Animais , Humanos , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Aspergillus , Fungos , Antineoplásicos/química , Antraquinonas/farmacologia , Estrutura MolecularRESUMO
The new polyketides lopouzanones A and B, as well as the new 1-O-acetyl and 2-O-acetyl derivatives of dendrodochol B, were isolated from the sponge-derived marine fungus Lopadostoma pouzarii strain 168CLC-57.3. Moreover, six known polyketides, gliorosein, balticolid, dendrodolide G, dihydroisocoumarine, (-)-5-methylmellein, and dendrodochol B, were identified. The structures of the isolated compounds were determined by a combination of NMR and ESIMS techniques. The absolute configurations of the lopouzanones A and B were determined using the Mosher's method. The cytotoxicity of the isolated compounds against human prostate cancer cells PC-3 and normal rat cardiomyocytes H9c2 was investigated. Gliorosein showed weak DPPH radical-scavenging activity and in vitro cardioprotective effects toward rotenone toxicity and CoCl2-mimic hypoxia.
Assuntos
Ascomicetos , Policetídeos , Humanos , Ratos , Animais , Policetídeos/química , Ascomicetos/química , Espectroscopia de Ressonância Magnética/métodos , Estrutura MolecularRESUMO
Chemical investigation of a coculture of the marine-derived fungi Beauveria felina KMM 4639 and Aspergillus carneus KMM 4638 led to the identification of three new drimane-type sesquiterpenes, asperflavinoids B, D and E (2, 4, 5), and nine previously reported related compounds. The structures of these compounds were established using spectroscopic methods and by comparison with known analogues. We also investigated the cytotoxic activity of the isolated compounds against several cancer and normal cell lines. Asperflavinoid C (3) and ustusolate E (9) exerted a significant effect on human breast cancer MCF-7 cell viability, with IC50 values of 10 µM, and induced in caspase-dependent apoptosis and arrest of the MCF-7 cell cycle in the G2/M phase in these cells.
Assuntos
Antineoplásicos , Beauveria , Sesquiterpenos , Antineoplásicos/química , Aspergillus , Beauveria/química , Linhagem Celular Tumoral , Técnicas de Cocultura , Humanos , Estrutura Molecular , Sesquiterpenos Policíclicos , Sesquiterpenos/químicaRESUMO
Three new glycosylated secondary metabolites, including a new indole alkaloid, pityriacitrin D (1), and two new trehalose lipids (2 and 3), together with three known compounds (4-6) were isolated from two marine-derived bacterial strains, Bacillus siamensis 168CLC-66.1 and Tsukamurella pseudospumae IV19-045. The structures of 1-3 were determined by extensive analysis and comparison of their spectroscopic data with literature values. The absolute configurations of sugar moieties were determined by chemical derivatization followed by LC-MS analysis. Cytotoxicity of 1-3 against six cancer cell lines was evaluated by SRB assay, and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 8.0 to 10.9 µM.
Assuntos
Actinomycetales , Bactérias , Estrutura MolecularRESUMO
Three new tripeptide derivatives asterripeptides A-C (1-3) were isolated from Vietnamese mangrove-derived fungus Aspergillus terreus LM.5.2. Structures of isolated compounds were determined by a combination of NMR and ESIMS techniques. The absolute configurations of all stereocenters were determined using the Murfey's method. The isolated compounds 1-3 contain a rare fungi cinnamic acid residue. The cytotoxicity of isolated compounds against several cancer cell lines and inhibition ability of sortase A from Staphylococcus aureus of asterripeptides A-C were investigated.
Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Aspergillus , Magnoliopsida , Peptídeos/farmacologia , Animais , Antibacterianos/química , Antineoplásicos/química , Organismos Aquáticos , Linhagem Celular Tumoral , Humanos , Testes de Sensibilidade Microbiana , Peptídeos/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Three new polyene compounds, talacyanols A-C (1-3), along with two known compounds, ramulosin (4) and eurothiocin A (5), were isolated from the marine fungus Talaromyces cyanescens derived from a seaweed Caulerpa sp. Structures of 1-5 were established by one-dimensional and two-dimensional (1D/2D) NMR, HR-ESIMS, and the modified Mosher's methods, as well as comparison with previously reported literature data. All the compounds (1-5) were tested for their in vitro cytotoxic and anti-neuroinflammatory activities. Among them, 1 showed moderate cytotoxic activity against a panel of cancer cell lines (HCT-15, NUGC-3, NCI-H23, ACHN, PC-3, and MDA-MB-231) with GI50 values ranging from 44.4 to 91.6 µM, whereas compounds 2 and 5 exhibited anti-neuroinflammatory effect without cytotoxicity against all the tested cell lines.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Polienos/farmacologia , Talaromyces/química , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Polienos/uso terapêuticoRESUMO
The red alga Kappaphycus striatus is economically important food species and extensively cultivated throughout most tropical parts of the world as a source of carrageenan. In this note, the primary structure of a new lectin KSL from this alga was elucidated by the rapid amplification method of complementary DNA (cDNA) ends, which consists of 267 amino acid residues distributed in four tandem-repeated domains of about 67 amino acids and sharing 43% of identity. The calculated molecular mass from the deduced sequence was consistent with that of natural KSL (27,826 Da) determined by electron spray ionization-mass spectrometry. The primary structure of KSL showed high similarity to those of the high mannose N-glycan specific lectins from marine red algae, ESA-2 from Eucheuma serra, EDA-2 from Eucheuma denticulatum, KSA-2 from Kappaphycus striatum, KAAs from Kappaphycus alvarezii and SfLs from Solieria filiformis, and from microorganisms, BOA from Burkholderia oklahomensis, MBHA from Myxococcus xanthus, OAA from Oscillatoria agardhii and PFL from Pseudomonas fluorescens. Furthermore, KSL showed anticancer effects against five carcinoma cell lines, HT29, Hela, MCF-7, SK-LU-1 and AGS, in a dose-dependent manner with the IC50 values of 0.80-1.94 µM, whereas its inhibition activities on cancer cells were not detected in the presence of yeast mannan, an inhibitor against lectin KSL. The cultivated red alga K. striatus could also be a good source of functional lectin(s) for application as anticancer agents.
Assuntos
Antineoplásicos/uso terapêutico , Lectinas/química , Rodófitas/química , Antineoplásicos/farmacologia , Humanos , Estrutura MolecularRESUMO
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
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
Five new sesterterpenes, 14,15-dehydro-6-epi-ophiobolin K (1), 14,15-dehydro- ophiobolin K (2), 14,15-dehydro-6-epi-ophiobolin G (3), 14,15-dehydro-ophiobolin G (4) and 14,15-dehydro-(Z)-14-ophiobolin G (5), together with four known ophiobolins (6-9) were isolated from the marine fungus Aspergillus flocculosus derived from the seaweed Padina sp. collected in Vietnam. The five new ophiobolins were first isolated as ophiobolin derivatives consisting of a fully unsaturated side chain. Their structures were elucidated via spectroscopic methods including 1D, 2D NMR and HR-ESIMS. The absolute configurations were determined by the comparison of chemical shifts and optical rotation values with those of known ophiobolins. All compounds (1-9) were then evaluated for their cytotoxicity against six cancer cell lines, HCT-15, NUGC-3, NCI-H23, ACHN, PC-3 and MDA-MB-231. All the compounds showed potent cytotoxicity with GI50 values ranging from 0.14 to 2.01 µM.
Assuntos
Organismos Aquáticos/química , Aspergillus/química , Fungos/química , Sesterterpenos/química , Sesterterpenos/farmacologia , Linhagem Celular Tumoral , Humanos , Células PC-3 , Alga Marinha/microbiologia , VietnãRESUMO
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
A new α-pyrone merosesquiterpenoid possessing an angular tetracyclic carbon skeleton, ochraceopone F (1), and four known secondary metabolites, aspertetranone D (2), cycloechinulin (3), wasabidienone E (4), and mactanamide (5), were isolated from the marine fungus Aspergillus flocculosus derived from a sponge Stylissa sp. collected in Vietnam. The structures of Compounds 1-5 were elucidated by analysis of 1D and 2D NMR spectra and MS data. All the isolated compounds were evaluated for anti-proliferation activity and their suppression effects on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation using tartate-resisant acid phosphatase (TRAP). Compounds 1-5 had no anti-proliferative effect on human cancer cell lines up to 30 µg/mL. Among these compounds, aspertetranone D (2) and wasabidienone E (4) exhibited weak osteoclast differentiation inhibitory activity at 10 µg/mL. However, mactanamide (5) showed a potent suppression effect of osteoclast differentiation without any evidence of cytotoxicity.