Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances

Journal of Enzyme Inhibition and Medicinal Chemistry

Anderson S. Pinheiro¹  Danielle M. P. Oliveira¹  Jéssica B. Jesus²  Alessandra M. T. Souza²  Ana Carolina Rennó Sodero²  Alane B. Vermelho³  Ana Claudia F. Amaral⁴  Andreza R. Garcia⁵  Igor A. Rodrigues⁶  Claudiu T. Supuran⁷ 

[1] Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Department of Drugs and Medicines, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Department of General Microbiology, Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Department of Natural Products, Farmanguinhos, FIOCRUZ, Rio de Janeiro, Brazil;Graduate Program in Pharmaceutical Sciences, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Graduate Program in Pharmaceutical Sciences, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;Department of Natural Products and Food, School of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazi;Neurofarba Department, Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche, Florence, Italy;

关键词: Leishmania infantum;    visceral leishmaniasis;    arginase;    inhibitor;    rosmarinic acid;    caffeic acid;   

DOI  :  10.1080/14756366.2019.1616182

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY