a Graduate Program in Pharmaceutical Sciences , School of Pharmacy, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
b Department of Biochemistry , Institute of Chemistry, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):1100-1109. doi: 10.1080/14756366.2019.1616182.
Inhibition of 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 arginase (ARGLi) and investigated their antileishmanial activity . ARGLi exhibited a of 0.28 ± 0.016 mM/min and a 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 with IC 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.
精氨酸酶的抑制作用导致寄生虫生长和感染力降低，因此代表了一种有吸引力的治疗策略。我们评估了选定的天然存在的酚类物质对精氨酸酶（ARGLi）的抑制潜力，并研究了它们的抗利什曼原虫活性。ARGLi 对 L-精氨酸的 为 0.28±0.016 mM/min， 为 5.1±1.1 mM。苯丙素类化合物迷迭香酸和咖啡酸（100 μM）的抑制率分别为 71.48±0.85%和 56.98±0.51%。此外，迷迭香酸和咖啡酸对 的作用最大，其对前鞭毛体的 IC 值分别为 57.3±2.65 和 60.8±11 μM，对细胞内无鞭毛体的 IC 值分别为 7.9±1.7 和 21.9±5.0 μM。只有咖啡酸能显著增加感染巨噬细胞的一氧化氮产生。总的来说，我们的结果拓宽了已知精氨酸酶抑制剂的范围，并为内脏利什曼病的治疗提供了有前途的候选药物。
