RESUMO
Two new phenylspirodrimane derivatives, stachybotrysin (1) and stachybotrylactone B (2), were isolated from the cultures of the marine-derived fungus Stachybotrys sp. KCB13F013. The structures were determined by analyzing the spectroscopic data (1D and 2D NMR and MS) and chemical transformation, including the modified Mosher's method and single-crystal X-ray structure analysis. Compound 1 exhibited an inhibitory effect on osteoclast differentiation in bone marrow macrophage cells via suppressing the RANKL-induced activation of p-ERK, p-JNK, p-p38, c-Fos, and NFATc1.
Assuntos
Osteoclastos/efeitos dos fármacos , Stachybotrys/química , Animais , Células da Medula Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Técnicas de Cocultura , Regulação para Baixo/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Biologia Marinha , Camundongos , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , Osteoblastos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/genética , Ligante RANK/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Salterns, one of the most extreme natural hypersaline environments, are a rich source of halophilic and halotolerant microorganisms, but they remain largely underexplored ecological niches in the discovery of bioactive secondary metabolites. In continued efforts to investigate the metabolic potential of microbial populations from chemically underexplored sites, three new lipopeptides named iturin F1, iturin F2 and iturin A9 (1-3), along with iturin A8 (4), were isolated from Bacillus sp. KCB14S006 derived from a saltern. The structures of the isolated compounds were established by 1D-, 2D-NMR and HR-ESIMS, and their absolute configurations were determined by applying advanced Marfey's method and CD spectroscopy. All isolates exhibited significant antifungal activities against various pathogenic fungi and moderate cytotoxic activities toward HeLa and src(ts)-NRK cell lines. Moreover, in an in vitro enzymatic assay, compound 4 showed a significant inhibitory activity against indoleamine 2,3-dioxygenase.