RESUMEN
The research on resveratrol (1) has been conducted intensively over a long time due to its proven antioxidant activity and disease-fighting capabilities. Many efforts have also been made to increase these biological effects. In the present study, six new extended aromatic resveratrol analogues containing naphthalene (2) and its bioisosteres quinoline (3 and 4), isoquinoline (5) quinoxaline (6) and quinazoline (7) scaffolds were designed and synthesized using an annulation strategy. The antioxidant and anti-inflammatory activities of these compounds were investigated. All compounds showed better antioxidant activity than resveratrol in ABTS assay. As for the anti-inflammatory test, 5 and 7 exhibited better activity than resveratrol. It is worth noting that nitrogen substitution on the extended aromatic resveratrol analogues has a significant impact on cell viability. Taking the antioxidant activities and NO inhibition activities into consideration, we conclude that isoquinoline analogue 5 may qualify for the further investigation of antioxidant and anti-inflammatory therapy. Furthermore, our study results suggest that in order to improve the biological activity of polyphenolic compounds, extended aromaticity and nitrogen substitution strategy could be a viable method for the design of future drug candidates.
Asunto(s)
Antioxidantes/síntesis química , Interleucina-1beta/genética , Interleucina-6/genética , Lipopolisacáridos/efectos adversos , Resveratrol/análogos & derivados , Estilbestroles/síntesis química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Supervivencia Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Isoquinolinas/química , Ratones , Naftalenos/química , Quinazolinas/química , Quinolinas/química , Quinoxalinas/química , Células RAW 264.7 , Resveratrol/química , Estilbestroles/química , Estilbestroles/farmacología , Relación Estructura-ActividadRESUMEN
We had observed in our previous study that the active fucoidan (JHCF4), isolated from the crude fucoidan in acid-processed Hizikia fusiforme, possessed an anticancer effect. In this study, the antioxidant effect of JHCF4 was evaluated. Among the fractions, JHCF4 showed the highest scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH), alkyl, and hydroxyl radicals, as well as protective effect against reactive oxygen species (ROS) in 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-treated Vero cells. Furthermore, JHCF4 showed a protective activity against AAPH-induced apoptosis, as observed by nuclear staining with Hoechst 33342. Our results showed that JHCF4 can up-regulate Bcl-xL, down-regulate Bax and cleave caspase-3 with increased concentrations in AAPH-induced Vero cells. JHCF4 induced anti-apoptosis via a mitochondria-mediated pathway. Additionally, JHCF4 was selected for further in vivo screening in a zebrafish model, which markedly decreased ROS generation and lipid peroxidation. Thus, JHCF4 showed a potential protective activity against AAPH-induced ROS both in vitro and in the zebrafish model.
Asunto(s)
Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/farmacología , Sargassum/química , Amidinas/química , Animales , Antioxidantes/farmacología , Compuestos de Bifenilo/química , Caspasa 3/metabolismo , Línea Celular , Chlorocebus aethiops , Regulación hacia Abajo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Picratos/química , Sustancias Protectoras/farmacología , Especies Reactivas de Oxígeno/metabolismo , Estilbestroles/química , Regulación hacia Arriba/efectos de los fármacos , Células Vero , Pez Cebra , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Lignins from different tree barks, including Norway spruce (Picea abies), eucalyptus (Eucalyptus globulus), mimosa (Acacia dealbata) and blackwood acacia (A. melanoxylon), are thoroughly characterized. The lignin from E.â globulus bark is found to be enriched in syringyl (S) units, with lower amounts of guaiacyl (G) and p-hydroxyphenyl (H) units (H/G/S ratio of 1:26:73), which produces a lignin that is highly enriched in ß-ether linkages (83 %), whereas those from the two Acacia barks have similar compositions (H/G/S ratio of ≈5:50:45), with a predominance of ß-ethers (73-75 %) and lower amounts of condensed carbon-carbon linkages; the lignin from A.â dealbata bark also includes some resorcinol-related compounds, that appear to be incorporated or intimately associated to the polymer. The lignin from P.â abies bark is enriched in G units, with lower amounts of H units (H/G ratio of 14:86); this lignin is thus depleted in ß-O-4' alkyl-aryl ether linkages (44 %) and enriched in condensed linkages. Interestingly, this lignin contains large amounts of hydroxystilbene glucosides that seem to be integrally incorporated into the lignin structure. This study indicates that lignins from tree barks can be seen as an interesting source of valuable phenolic compounds. Moreover, this study is useful for tailoring conversion technologies for bark deconstruction and valorization.