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 V-max of 0.28 +/- 0.016 mM/min and a K-m of 5.1 +/- 1.1 mM for L-arginine. The phenylpropanoids rosmarinic acid and caffeic acid (100 mu M) 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 mu M for promastigotes, and 7.9 +/- 1.7 and 21.9 +/- 5.0 mu M 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.
Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances / Garcia, Andreza R; Oliveira, Danielle M P; Claudia F Amaral, Ana; Jesus, Jéssica B; Rennó Sodero, Ana Carolina; Souza, Alessandra M T; Supuran, Claudiu T; Vermelho, Alane B; Rodrigues, Igor A; Pinheiro, Anderson S. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - ELETTRONICO. - 34:(2019), pp. 0-0. [10.1080/14756366.2019.1616182]
Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances
Supuran, Claudiu T;
2019
Abstract
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 V-max of 0.28 +/- 0.016 mM/min and a K-m of 5.1 +/- 1.1 mM for L-arginine. The phenylpropanoids rosmarinic acid and caffeic acid (100 mu M) 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 mu M for promastigotes, and 7.9 +/- 1.7 and 21.9 +/- 5.0 mu M 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.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.