Nitric oxide inhibitory activity of hydrogenated synthetic analogues of furanonaphthoquinones isolated from Tabebuia spp.

Objective: to describe the synthesis of analogues of furanonaphthoquinones isolated from Tabebuia genus and their inhibitory effect on nitric oxide production. Methods: a series of six derivatives were prepared through cycloaddition reactions and the products characterized by spectroscopy methods. The biological activity was evaluated measuring their effect on the pro-inflammatory mediator production in macrophages RAW 264.7 induced with lipopolysaccharides. To prevent compounds from interfering with cellular viability, their cytotoxic effect was determined using methyl tetrazolium assay. Additionally, scavenging effect was in vitro measured. Results: FNQ1, FNQ2, and FNQ5 derivatives showed potent concentration-depending inhibitory effect on nitric oxide production, with an IC50 value lower than 2 µM concentration at which they did not have toxic or scavenging effects. FNQ5 was the most active and selective derivative. Conclusions: this is the first paper concerning the anti-inflammatory potential of tested synthetic compounds. Our results indicated that FNQ5 might be considered as useful potential anti-inflammatory molecule to treat inflammatory diseases related with nitric oxide overproduction.(AU) Objetivo: describir la sintesis de analogos de furanonaftoquinonas aisladas del genero Tabebuia y su efecto inhibidor en la produccion de oxido nitrico. Metodos: se obtuvo una serie de seis derivados a traves de reacciones de cicloadicion y se caracterizaron los productos por metodos espectroscopicos. Se evaluo la actividad biologica por su efecto en la produccion del mediador proinflamatorio en macrofagos RAW 264.7 activados con lipopolisacarido. Para asegurar que los compuestos no interfirieran con la viabilidad celular, se evaluo su efecto citotoxico empleando el ensayo de metiltetrazolio. Adicionalmente, se evaluo el efecto captador del radical in vitro. Resultados: los derivados FNQ1, FNQ2 y FNQ5 demostraron potente efecto inhibitorio en la produccion de oxido nitrico de manera concentracion-dependiente, con un valor de CI50 menor que 2 µM, concentracion a la que no ejercieron efectos toxicos o captadores de radicales. FNQ5 resulto el compuesto mas activo y selectivo. Conclusiones: este trabajo es el primero que evalua el potencial antinflamatorio de los compuestos sintetizados. Los resultados indican que FNQ5 puede ser considerada como una molecula de uso potencial para el tratamiento de enfermedades inflamatorias que cursen con sobreproduccion de oxido nitrico.(AU)