RESUMEN
Herein we report the anti-inflammatory activity of lobaric acid and pseudodepsidones isolated from the nordic lichen Stereocaulon paschale. Lobaric acid (1) and three compounds (2, 7 and 9) were found to inhibit the NF-κB activation and the secretion of pro-inflammatory cytokines (IL-1ß and TNF-α) in LPS-stimulated macrophages. Inhibition and docking simulation experiments provided evidence that lobaric acid and pseudodepsidones bind to PPAR-γ between helix H3 and the beta sheet, similarly to partial PPAR-γ agonists. These findings suggest that lobaric acid and pseudodepsidones reduce the expression of pro-inflammatory cytokines by blocking the NF-κB pathway via the activation of PPAR-γ.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Depsidos/farmacología , Lactonas/farmacología , Líquenes/química , FN-kappa B/antagonistas & inhibidores , PPAR gamma/agonistas , Salicilatos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Depsidos/química , Depsidos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Humanos , Lactonas/química , Lactonas/aislamiento & purificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Simulación del Acoplamiento Molecular , Estructura Molecular , FN-kappa B/metabolismo , PPAR gamma/metabolismo , Salicilatos/química , Salicilatos/aislamiento & purificación , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Células U937RESUMEN
Chemical investigation of the methanol extract of the lichen Stereocaulon paschale collected in Nunavik, Canada, led to the isolation and identification of two new dibenzofurans (1 and 3) and 11 known lichen metabolites. The structures of the new compounds were established by analysis of 1D and 2D NMR spectroscopic and high-resolution mass spectrometric data. Herein, the first isolation of ascomatic acid dibenzofuran derivatives (1-3) from a whole lichen organism is reported. In addition, some of the isolated metabolites showed antibacterial activity against the oral pathogens Porphyromonas gingivalis and Streptococcus mutans.
Asunto(s)
Antibacterianos/aislamiento & purificación , Dibenzofuranos/aislamiento & purificación , Dibenzofuranos/farmacología , Líquenes/química , Porphyromonas gingivalis/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Canadá , Dibenzofuranos/química , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Streptococcus mutansRESUMEN
A novel 21-residue peptide incorporating six fluorinated amino acids was prepared. It was designed to fold into an amphiphilic alpha helical structure of nanoscale length with one hydrophobic face and one fluorinated face. The formation of a fluorous interface serves as the main vector for the formation of a superstructure in a bilayer membrane. Fluorescence assays showed this ion channel's ability to facilitate the translocation of alkali metal ions through a phospholipid membrane, with selectivity for sodium ions. Computational studies showed that a tetramer structure is the most probable and stable supramolecular assembly for the active ion channel structure. The results illustrate the possibility of exploiting multiple Fδ-:M+ interactions for ion transport and using fluorous interfaces to create functional nanostructures.
