Synthesis and biological evaluation of 8-hydroxy-2,7-naphthyridin-2-ium salts as novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

By analogy with the natural product chelerythrine, which has been identified as an inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), we prepared a small series of 8-hydroxy-2,7-naphthyridin-2-ium salts. Spectroscopic analyses allowed us to elucidate the zwitterionic nature of 2,7-naphthyridin-1(7H)-ones, the neutral state of 8-hydroxy-2,7-naphthyridin-2-ium salts. Among the tested compounds, we identified dual inhibitors of AChE and BChE as well as an inhibitor showing a preferential inhibition of AChE over BChE. By in vitro characterization in combination with docking studies, we were able to identify structural features that influence the biological activity of 8-hydroxy-2,7-naphthyridin-2-ium salts.

Actividad antioxidante y polifenoles de las algas marinas halimeda opuntia y halimeda monile / No disponible

En este trabajo se estudió la actividad antioxidante de dos especies de algas marinas (H. opuntia y H. monile) mediante el ensayo de atrapamiento de radicales DPPH• y el sistema β-Caroteno-acido linoleico. Adicionalmente a las fracciones de ácidos fenolicos libres, ésteres solubles y ésteres insolubles de ácidos fenólicos se les determinó el contenido en fenoles totales mediante la técnica de Folin-Ciocalteu y posteriormente se identificaron y cuantificaron 8 ácidos fenólicos y cinámicos, resultando el componente mayoritario el ácido salicílico. En los ensayos utilizados se obtuvieron valores altos de actividad antioxidante para las diferentes fracciones. A partir de estos resultados se puede postular que la actividad antioxidante de los extractos polares de estas algas pudiera ser explicada, al menos parcialmente, por la presencia de los ácidos fenólicos y cinámicos. En el caso del alga Halimeda monile, de acuerdo con la literatura consultada, es el primer reporte de la actividad antioxidante(AU)

In this paper, the antioxidant activity displayed by two different green seaweed species (H. opuntia y H. monile) was studied using the β- carotene/ linoleic acid and the DPPH• scavenging.systems as different experimental in vitro antioxidant assessment models. Polar seaweed fractions containing free phenolic acids, soluble esters and insoluble esters of phenolic acids were chemically characterized in terms of their phenolic content and composition. In that direction, 8 phenolic acids were identified and quantified, and salycilic acid was shown to be the majoritary compound on the fractions from both species. In addition, the polar fractions were proved to exert antioxidant activity in the two used experimental systems with considerably low values of CI50. Thus, in view of these findings, the antioxidant activity of these polar Halimeda spp. extracts could be supported and at least partially related to the presence of phenolic acids. In case of Halimeda monile this is, at least to the extend of our knowledge, the first report of such biological activity(AU)

Effects of the aqueous extract of Bryothamnion triquetrum on chemical hypoxia and aglycemia-induced damage in GT1-7 mouse hypothalamic immortalized cells.

The neuroprotective ability of the aqueous crude extract of Bryothamnion triquetrum (S. G. Gmelin) Howe and its cinnamic acids was studied in GT1-7 cells exposed to the combination of chemical hypoxia (KCN 3 mM) and aglycemia conditions. These ischemia-like conditions provoked acute and delayed cytotoxicity in GT1-7 cells if extended for more than 90 min. The extract was able to protect from the cell death produced by severe (180 min) chemical hypoxia/aglycemia insult, which cannot be related to its glucose content, and also reduced the cytotoxicity and early production of free radicals produced by mild (105 min) insult. Results showed that some of these protective effects of the extract are partially related to the presence of ferulic acid. The data additionally suggest that neuroprotection exerted by the extract is related to its ability to reduce free-radical generation by mechanisms different from the direct scavenging of the radical entities.

Effects of aqueous extracts of Halimeda incrassata (Ellis) Lamouroux and Bryothamnion triquetrum (S.G.Gmelim) Howe on hydrogen peroxide and methyl mercury-induced oxidative stress in GT1-7 mouse hypothalamic immortalized cells.

The current investigation focuses attention on the neuroprotective and antioxidant properties of aqueous extracts from Halimeda incrassata (Hi) and Bryothamniom triquetrum (Bt) in the mouse immortalized hypothalamic GT1-7 cell line. Under basal oxidative conditions, Hi extract reduces intracellular reactive oxygen species production, as assessed by 2',7'-dichlorofluorescein fluorescence, while Bt extract does not contribute to basal ROS generation. Both extracts, at concentrations higher than 0.20 mg/ml, exert protection against hydrogen peroxide-mediated cell death, although only Hi extract can additionally prevent hydrogen peroxide-induced ROS production. The two seaweed aqueous extracts, at concentrations higher than 0.05 mg/ml, also display protection against neuronal death induced by methyl mercury chloride, as well as against methyl mercury chloride-mediated ROS generation. None of the extracts increase GSH intracellular pools, in basal conditions, after depleting its levels with either hydrogen peroxide or methyl mercury chloride. Some comments on the probable targets of the neuroprotection exerted by these two extracts are included in this paper.