RESUMO
Two unique nitrogenous sesquiterpene quinone meroterpenoids, dysidinoid B (1) and dysicigyhone A (2), together with eight known analogues (3-10) were isolated and characterized from the marine sponge Dysidea septosa. Their structures with absolute configurations were established by a combination of extensive spectroscopic, electron circular dichroism (ECD) and single-crystal X-ray diffraction data analysis. Structurally, dysicigyhone A (2) possessed a unique benzo[d]oxazolidine-2-one unit. Additionally, dysidinoid B (1) exhibited significant anti-inflammatory effect by inhibiting TNF-α and IL-6 generation with IC50 values of 9.15 µM and 17.62 µM, respectively. Further in vivo anti-inflammatory assay verified that the dysidinoid B (1) alleviated the CuSO4-induced robust acute inflammatory response in zebrafish model.
Assuntos
Anti-Inflamatórios/farmacologia , Benzoquinonas/farmacologia , Inflamação/tratamento farmacológico , Nitrogênio/farmacologia , Poríferos/química , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Benzoquinonas/química , Células Cultivadas , Sulfato de Cobre , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Descoberta de Drogas , Humanos , Inflamação/induzido quimicamente , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Camundongos , Modelos Moleculares , Estrutura Molecular , Nitrogênio/química , Células RAW 264.7 , Sesquiterpenos/química , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossíntese , Peixe-ZebraRESUMO
The chemical investigation of the marine sponge Dysidea frondosa discovered a pair of unprecedented bioconjugates that are composed of a meroterpene and an unusual psammaplysin alkaloid. The structures of frondoplysins A (1) and B (2) were characterized by analysis of HRMS and NMR data coupled with single-crystal X-ray diffraction. Frondoplysin A was found to be a potent inhibitor targeting protein-tyrosine phosphatase 1B (PTP1B) with an IC50 value of 0.39 µM.
Assuntos
Alcaloides/química , Dysidea/química , Inibidores Enzimáticos/farmacologia , Alcaloides/farmacologia , Alcaloides/toxicidade , Animais , Animais Geneticamente Modificados , Antioxidantes/química , Antioxidantes/farmacologia , Cristalografia por Raios X , Inibidores Enzimáticos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Peixe-Zebra/genéticaRESUMO
Three unusual meroterpenoids, septosones A-C (1-3), were isolated from the marine sponge Dysidea septosa. The structures were determined by analysis of spectroscopic data combined with single-crystal X-ray diffraction and ECD calculations. Septosone A (1) features an unprecedented "septosane" carbon skeleton, whereas septosones B (2) and C (3) share a rare spiro[4.5]decane motif. Septosone A showed in vivo anti-inflammatory activity in CuSO4-induced transgenic fluorescent zebrafish likely through inactivation of the NF-κB signaling pathway.
Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Carbono/química , Dysidea/química , Terpenos/química , Terpenos/farmacologia , Animais , Células HEK293 , Humanos , Modelos Moleculares , Conformação Molecular , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-ZebraAssuntos
Antineoplásicos/farmacologia , Aspergillus/química , Dicetopiperazinas/farmacologia , Poríferos/microbiologia , Animais , Antineoplásicos/química , Aspergillus/isolamento & purificação , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13/normas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dicetopiperazinas/química , Dimerização , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Conformação Molecular , Padrões de ReferênciaRESUMO
A novel aerobic, spore-forming, marine actinomycete, designated strain LHW63015T, was isolated from a Craniella marine sponge collected in the South China Sea. The strain formed extensively branched substrate and aerial mycelia which carried long and crooked spore chains composed of ridged spores and spherical pseudosporangia. Strain LHW63015T contained meso-diaminopimelic acid as the diagnostic diamino acid. Glucose, ribose, mannose, galactose and madurose occured in whole-cell hydrolysates. The predominant polar lipids were hydroxyl-phosphatidylethanolamine, phosphoglycolipid and ninhydrin-positive phosphoglycolipid. MK-10(H4) and MK-10(H6) were the predominant menaquinones. The major fatty acids were 10-methyl C17â:â0 and C17â:â1ω8c. The G+C content of the genomic DNA was 70.8 mol%. In phylogenetic analysis based on 16S rRNA gene sequences, strain LHW63015T fell within the family Streptosporangiaceae and formed a distinct monophyletic lineage adjacent to the genus Sphaerisporangium, and shared the highest 16S rRNA gene sequence similarity of 96.2â% with Sphaerisporangium album YIM 48782T. On the basis of the polyphasic evidence, a novel genus and species of the family Streptosporangiaceae, for which the name Spongiactinospora rosea gen. nov., sp. nov., is proposed, with the type strain LHW63015T (=DSM 106635T=CCTCC AA 2018019T).
