Dados do Trabalho

Título

Curcumin Coordinated by Transition Metals as Inhibitors of Leishmania infantum Arginase

Introdução

Arginase is a metalloenzyme involved in polyamine biosynthesis by producing L-ornithine and urea. Inhibiting arginase restricts spermidine synthesis, which is crucial for the parasite's growth, survival and trypanothione production, therefore making it a promising target for developing new anti-Leishmania drugs. Curcuminoids, the active components of Curcuma longa, display potent anti-leishmanial activity, but their mechanisms remain elusive. Notably, their ability to form metal complexes makes them promising starting points for developing highly bioactive coordination compounds (CCMs).

Objetivo (s)

This study aims to evaluate the anti-L. infantum effect of curcumin coordinated by transition metals targeting the inhibition of the L. infantum arginase (LiARG).

Material e Métodos

Viability in Leishmania infantum promastigotes was verified using the resazurin assay and viability in RAW 264.7 was verified using the MTT assay. Both treated for 48 h with different concentrations of CCMs. The 50% inhibitory concentration (IC50) for the parasite and the 50% cytotoxic concentration (CC50) for the host cell were calculated through regression analysis. Hemolysis was performed with red blood cells (061/22-CEUA/UFRJ) and measured at 570 nm. Recombinant LiARG was obtained through the expression of a heterologous protein and was purified by nickel affinity chromatography. The activity of LiARG was determined based on urea dosage after enzymatic reaction with the substrate in the presence of CCMs [100 µM].

Resultados e Conclusão

The isolated curcumin (C1) demonstrated an IC50 of 6.9µM ± 0.4, with Cu2+ (C2) was 7.74µM ± 1.25, with Zn2+ and Ni2+ was <3,125µM. The samples did not exhibit hemolytic effects at the highest concentration tested (400 µM). The CC50  values for C1 and C2 were 61.8µM ± 5.9 and 31.4µM ± 0.9. The samples were able to inhibit LiARG, with the percentages being 39.64%± 6.4 (C1) and 68% ± 3.4 (C2). Thus, coordination with copper enhanced the inhibitory activity of curcumin on LiARG. Similar analyses are ongoing for the other CCMs, as well as the test on amastigotes forms of L. infantum.

Palavras Chave

Visceral Leishmaniasis; coordination compounds; enzymatic inhibition