RESUMEN
Nigrograna sp. LY66, an endophytic fungus associated with the herbal medicinal plant Clematis shensiensis, produced four undescribed steroids, nigergostanes A-D (1-4), including an unusual ketal-containing nigergostane (1), and four undescribed sesquiterpenoids decorated with cyclohexanone motifs, nigbisabolanes A-D (7-10), along with three known compounds, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (5), ergosta-5,7,22-trien-3ß-ol (6), and curculonone A (11). The structures and absolute configurations of these undescribed compounds were confirmed using spectroscopic data (NMR and HRESIMS), modified Mosher's method, and ECD experiments. Additionally, compounds 5 and 8 displayed significant inhibition of nitric oxide generation in lipopolysaccharide-induced BV-2 microglial cells with IC50 values of 2.8 and 2.7 µM, respectively, and is thus more potent than that of the positive control, quercetin (IC50 = 8.77 µM). A molecular docking study revealed that 23-OH of 5 binds to the Y347 residue of inducible nitric oxide synthase (iNOS), whereas the 2-OH and 9,10-diol moieties of 8 bind to R381 and W463 and haeme residues of iNOS, respectively, which has rarely been reported in previous studies. These findings provide a set of undescribed lead compounds that can be developed into anti-neuroinflammatory agents.
Asunto(s)
Ascomicetos , Clematis , Fitosteroles , Sesquiterpenos , Esteroles , Clematis/metabolismo , Simulación del Acoplamiento Molecular , Ascomicetos/metabolismo , Sesquiterpenos/farmacología , Sesquiterpenos/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Óxido NítricoRESUMEN
Phaeosphaeria fuckelii, an endophytic fungus associated with the herbal medicine Phlomis umbrosa, produced four new thiodiketopiperazine alkaloids, phaeosphaones A-D (1-4), featuring an unusual ß-(oxy)thiotryptophan motif, along with four known analogues, phaeosphaone E (5), chetoseminudin B (6), polanrazine B (7), and leptosin D (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. Compounds 4, 6, and 8 were found to display mushroom tyrosinase inhibitory activity with IC50 values of 33.2 ± 0.2, 31.7 ± 0.2, and 28.4 ± 0.2 µM, respectively, more potent than that of the positive control, kojic acid (IC50 = 40.4 ± 0.1 µM). A molecular-docking study disclosed the π-π stacking interaction between the indole moiety of 8 and the His243 residue of tyrosinase.
Asunto(s)
Alcaloides/química , Ascomicetos/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Agaricales , Cristalografía por Rayos X , Estructura MolecularRESUMEN
The endophytic fungus Guignardia mangiferae isolated from Ilex cornuta leaves was shown to produce a family of meroterpenes with toll-like receptor 3 regulating activity (1-9), of which 1-3 possessed new structures. The absolute stereochemistry of 1-3 was assigned through a combination of nuclear magnetic resonance experiments, chemical derivation, CD spectra, and single-crystal X-ray diffraction analyses (CuK α ). The precursor labeled cultivation suggests that these meroterpenes are most likely assembled through terpenoid-shikimate pathways. Moreover, meroterpenes 1-3, 5-7, and 9 selectively upregulate, but 4 and 8 downregulate the toll-like receptor 3 expression in mouse dendritic cells at 10.0 µM.
Asunto(s)
Ascomicetos/química , Ilex/microbiología , Terpenos/farmacología , Receptor Toll-Like 3/metabolismo , Endófitos , Regulación de la Expresión Génica , Estructura Molecular , Hojas de la Planta/microbiología , Terpenos/química , Terpenos/aislamiento & purificación , Receptor Toll-Like 3/químicaRESUMEN
Two new polyketides, arthropsadiol C (1) and massarilactone H (2), together with six known derivatives (3-8) were isolated from the culture broth of the marine-derived fungus Phoma herbarum. Their structures were elucidated on the basis of spectroscopic methods, including 2D NMR techniques. Compounds 2, 4, 5, and 8 showed moderate neuraminidase inhibitory activity with IC(50) values ranging from 4.15 to 9.16 µM.