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

Journal of Enzyme Inhibition and Medicinal Chemistry

Ana Claudia F. Amaral¹  Anderson S. Pinheiro²  Danielle M. P. Oliveira²  Alane B. Vermelho³  Andreza R. Garcia⁴  Igor A. Rodrigues⁴  Ana Carolina Rennó Sodero⁴  Alessandra M. T. Souza⁴  Jéssica B. Jesus⁴  Claudiu T. Supuran⁵ 

[1] Farmanguinhos, FIOCRUZ;Institute of Chemistry, Federal University of Rio de Janeiro;Institute of Microbiology Paulo de Goes, Federal University of Rio de Janeiro;School of Pharmacy, Federal University of Rio de Janeiro;Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche;

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

DOI  :  10.1080/14756366.2019.1616182

来源: DOAJ

【 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】

Unknown