RESUMO
Neuronal α4ß2 nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels (LGIC) that have been implicated in nicotine addiction, reward, cognition, pain disorders, anxiety, and depression. Nicotine has been widely used as a template for the synthesis of ligands that prefer α4ß2 nAChRs subtypes. The most important therapeutic use for α4ß2 nAChRs is as replacement therapy for smoking cessation and withdrawal and the most successful therapeutic ligands are partial agonists. In this case, we use the N-methylpyrrolidine moiety of nicotine to design and synthesize new α4ß2 nicotinic derivatives, coupling the pyrrolidine moiety to an aromatic group by introducing an ether-bonded functionality. Meta-substituted phenolic derivatives were used for these goals. Radioligand binding assays were performed on clonal cell lines of hα4ß2 nAChR and two electrode voltage-clamp experiments were used for functional assays. Molecular docking was performed in the open state of the nAChR in order to rationalize the agonist activity shown by our compounds.
Assuntos
Nicotina/química , Nicotina/farmacologia , Agonistas Nicotínicos/química , Agonistas Nicotínicos/farmacologia , Receptores Nicotínicos/química , Ligação Competitiva , Relação Dose-Resposta a Droga , Humanos , Cinética , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Nicotina/análogos & derivados , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
Filmy ferns are a conspicuous epiphytic component of the temperate rain forest of southern Chile and the more abundant genus is Hymenophyllum represented by 19 species, they are a primitive fern family sharing their limited water lost control (poikilohydricity) with lower non-vascular plants, such as bryophytes and lichens. Because, carbohydrate accumulation is a desiccation tolerance mechanism proposed for desiccation-tolerant vascularized plants, the aim of this investigation was to propose a methodology for soluble carbohydrate analysis in native ferns. Preparative- TLC showed to be a simple and rapid technique for separating Hymenophyllum sugars. GC-MS analysis allowed identifying glucitol (2.0 percent), sucrose (2.0 percent), alpha or beta-melibiose (5.0 percent) and salidroside (4.4 percent) in H. cruentum carbohydrate profile from H. dentatum showed significant differences presenting only two sugars sucrose (1.4 percent) and alpha or beta-melibiose (3.2 percent). Furthermore, salidroside, an antioxidant compound, was identified only in H. cruentum. Our results suggest that H. cruentum, has higher preventive mechanisms than H. dentatum; that would allow delay the effects of desiccation (prevent a rapid dehydration) and thus survive to short periods of drought present in the study area. Due to the presence of salidroside in H. cruentum this species should be more resistant to oxidative stress that H. dentatum.
Los helechos película se pueden encontrar en el bosque templado lluvioso del sur de Chile, siendo el género más abundante Hymenophyllum representado con 19 especies. Son una familia de helechos primitivos que comparten la limitación de control de pérdida de agua (poiquilohidrícos) con plantas no vasculares, tales como briófitas y líquenes. Como el contenido de hidratos de carbono ha sido asociado a la protección de la planta durante la desecación, su análisis es una herramienta importante para dilucidar el mecanismo asociado a este fenómeno. El objetivo de esta investigación fue proponer una metodología fácil y rápida para el análisis de hidratos de carbono en helechos nativos. La CCF-preparativa permitió la separación de hidratos de carbono presentes en plantas del género Hymenophyllum. El análisis por GC-MS logró identificar glucitol (2,0 por ciento), sacarosa (2,0 por ciento), alfa o Beta-melibiosa (5.0 por ciento) y salidrosido (4,4 por ciento) en H. cruentum. El perfil de hidratos de carbono de H. dentatum mostró diferencias significativas, mostrando sólo dos compuestos sacarosa (1,4 por ciento) y alfa o beta- melibiosa (3.2 por ciento). Además, salidrosido, un compuesto antioxidante, sólo fue identificado en H. cruentum. Nuestros resultados sugieren que ante la menor tolerancia a la desecación observada previamente en H. cruentum, esta especie presenta mecanismos que le permitirían retardar los efectos de la desecación (prevención de una rápida pérdida de agua) y así sobrevivir a los periodos cortos de sequía presentes en la zona de estudio. Debido a La presencia de salidrosido en H. cruentum, esta especie debería ser más resistente al estrés oxidativo que H. dentatum.
