RESUMEN
A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 µM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule.
Asunto(s)
Antimaláricos/síntesis química , Antimaláricos/farmacología , Óxido de Etileno/química , Óxido de Etileno/farmacología , Plasmodium falciparum/efectos de los fármacos , Quinonas/síntesis química , Quinonas/farmacología , Antimaláricos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Óxido de Etileno/síntesis química , Fibroblastos/efectos de los fármacos , Humanos , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Quinonas/química , Relación Estructura-ActividadRESUMEN
AbstractIn Amazonas State (Brazil), Justicia acuminatissima (Miq.) Bremek., Acanthaceae, leaf teas are used in folk medicine to treat several inflammatory illnesses. In order to validate this medicinal application, we analyzed the acute toxicity and antioxidant, antiedematogenic and antinociceptive potentials of an aqueous extract of this species, using culture cells and animal models. The aqueous extract did not cause toxic effects on human lymphocytes in high concentration (400 μg/ml), neither on mice treated with high doses (5000 mg/kg) in an acute toxicity analysis by oral route, and also did not cause lesions in the gastric mucosa of animals treated with 300 mg/kg, which was the maximal dose used in the anti-inflammatory screening. The aqueous extract caused inhibition of inflammatory pain in formalin-induced paw licking test with all tested doses, 30, 100 and 300 mg/kg, and antiedematogenic activity at 100 and 300 mg/kg. Additionally, the aqueous extract presented statistically significant action on the release of nitric oxide by lipopolysaccharide-activated macrophages. These results and other preliminary studies support the folk use of this species, and further investigation of its action mechanism by inhibition of COX-2 or related metabolite would be interesting.