RESUMO
Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3â nM.
Assuntos
Aureobasidium , Óxido Nítrico , Animais , Camundongos , Aureobasidium/química , Aureobasidium/metabolismo , Linhagem Celular , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Conformação Molecular , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , LactonasRESUMO
A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C (1-3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5-22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM.
Assuntos
Ácido Fusárico , Paecilomyces , Ácido Fusárico/farmacologia , Macrófagos , Anti-Inflamatórios , Estrutura MolecularRESUMO
Three new polyketides (penidihydrocitrinins A-C, 1-3) and fourteen known compounds (4-17) were isolated from the deep-sea-derived Penicillium citrinum W17. Their structures were elucidated by comprehensive analyses of 1D and 2D NMR, HRESIMS, and ECD calculations. Compounds 1-17 were evaluated for their anti-inflammatory and anti-osteoporotic bioactivities. All isolates exhibited significant inhibitory effects on LPS-stimulated nitric oxide production in murine brain microglial BV-2 cells in a dose-response manner. Notably, compound 14 displayed the strongest effect with the IC50 value of 4.7 µM. Additionally, compounds 6, 7, and 8 significantly enhanced osteoblast mineralization, which was comparable to that of the positive control, purmorphamine. Furthermore, these three compounds also suppressed osteoclastogenesis in a dose-dependent manner under the concentrations of 2.5 µM, 5.0 µM, and 10 µM.
Assuntos
Penicillium , Policetídeos , Animais , Camundongos , Policetídeos/farmacologia , Policetídeos/química , Estrutura Molecular , Penicillium/química , Anti-Inflamatórios/farmacologiaRESUMO
Aphidicolin, a potent DNA polymerase α inhibitor, has been explored in clinical trials for the treatment of cancer. So far, about 300 modified aphidicolins have been discovered. However, none have shown a stronger effect. Herein, we report 71 new (aphidicolins A1-A71, 1-71) and eight known (72-79) aphidicolin congeners from Botryotinia fuckeliana MCCC 3A00494, a fungus isolated from the western Pacific Ocean (-5572 m). The structures of 1-71 were determined through extensive spectroscopic analysis, X-ray crystallography, chemical derivatization, modified Mosher's method, and the ECD exciton chirality method. Compounds 54-57 and 58-64 are novel 6/6/5/6/5 pentacyclic aphidicolins featuring tetrahydrofuran and dihydrofuran rings, respectively, while compounds 65-71 are rare noraphidicolins. Aphidicolin A8 (8) significantly induced apoptosis in T24 (IC50 = 2.5 µM) and HL-60 (IC50 = 6.1 µM) cancer cells by causing DNA damage. By docking its structure to the human DNA polymerase α binding pocket, 8 was found to form tight intermolecular contacts, elaborating aphidicolin A8 as a potently cytotoxic lead compound.
Assuntos
Afidicolina/química , Botrytis/química , Biologia Marinha , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cristalografia por Raios X , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
To investigate structurally novel and anti-neuroinflammatory natural compounds from marine-derived microorganisms, the secondary metabolites of Aspergillus terreus Y10, a fungus separated from the sediment of the coast in the South China Sea, were studied. Three new compounds (2â»4), with novel open-ring butenolide skeletons, were isolated from the ethyl acetate extract of the culture medium. In addition, a typical new butenolide, asperteretal F (1), was found to dose-dependently inhibit tumor necrosis factor (TNF-α) generation with an IC50 of 7.6 µg/mL. The present study shows the existence of open-ring butenolides, and suggests that butenolides such as asperteretal F (1) are a promising new anti-neuroinflammatroy candidate for neurodegenerative diseases.
Assuntos
4-Butirolactona/análogos & derivados , Organismos Aquáticos/metabolismo , Aspergillus/metabolismo , Produtos Biológicos/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Linhagem Celular , Humanos , Concentração Inibidora 50 , Lipopolissacarídeos/imunologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Estrutura Molecular , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/imunologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fator de Necrose Tumoral alfa/imunologiaRESUMO
An improved four-step approach for the stereoselective synthesis of long-chain anti-2-amino-3-alkanols is described. Using this method, the syntheses of antiproliferative (antitumoral) compounds, spisulosine (ES-285, 2), clavaminols A and B (3 and 4), the deacetylated products of clavaminols H and N (7 and 8), as well as (2S,3R)-2-aminododecan-3-ol (9) and xestoaminol C (10), have been achieved in excellent diastereoselectivities. In vitro study showed that these compounds induced cell death and dose-dependently inhibited cell proliferation in human glioblastoma cell line SHG-44, indicating the anti-tumor property of this series of compounds.