RESUMEN
Inhibition of Leishmania arginase leads to a decrease in parasite growth and infectivity and thus represents an attractive therapeutic strategy. We evaluated the inhibitory potential of selected naturally occurring phenolic substances on Leishmania infantum arginase (ARGLi) and investigated their antileishmanial activity in vivo. ARGLi exhibited a Vmax of 0.28 ± 0.016 mM/min and a Km of 5.1 ± 1.1 mM for L-arginine. The phenylpropanoids rosmarinic acid and caffeic acid (100 µM) showed percentages of inhibition of 71.48 ± 0.85% and 56.98 ± 5.51%, respectively. Moreover, rosmarinic acid and caffeic acid displayed the greatest effects against L. infantum with IC50 values of 57.3 ± 2.65 and 60.8 ± 11 µM for promastigotes, and 7.9 ± 1.7 and 21.9 ± 5.0 µM for intracellular amastigotes, respectively. Only caffeic acid significantly increased nitric oxide production by infected macrophages. Altogether, our results broaden the current spectrum of known arginase inhibitors and revealed promising drug candidates for the therapy of visceral leishmaniasis.
Asunto(s)
Antiprotozoarios/farmacología , Arginasa/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Leishmania infantum/efectos de los fármacos , Fenoles/farmacología , Animales , Antiprotozoarios/química , Arginasa/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Leishmania infantum/enzimología , Leishmania infantum/crecimiento & desarrollo , Macrófagos/efectos de los fármacos , Macrófagos/parasitología , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Fenoles/química , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
The polymeric material in the latex of Himatanthus sucuuba (Spruce) Woodson was identified by spectroscopic methods as cis-polyisoprene (Mn = 192; Mw = 571; Mw/ Mn = 2.97). ICP-MS analysis of microelements in the aqueous phase showed the most abundant to be Ca (354 g/g) and Mg (250 g/g). Carbohydrate analysis of the aqueous phase by HPLC-PAD showed arabinose, glucose, xylose, rhamnose and galactose to be the predominant saccharides.
O polímero do látex de Himatanthus sucuuba (Spruce) Woodson foi identificado por métodos espectroscópicos como o cis-poliisopreno (Mn = 192; Mw = 571; Mw /Mn= 2.97). A análise de microelementos na fase aquosa por ICP-MS forneceu Ca (354 mg/g) e Mg (259 mg/g) como elementos majoritários. A detecção de carboidratos na fase aquosa por CLAE-DPA apresentou arabinose, glucose, xilose, ramnose e galactose como açúcares principais.
