Dados do Trabalho

Título

Phenolic compounds coordinated by copper: improvement of anti-Leishmania infantum action and arginase inhibition

Introdução

Visceral leishmaniasis is a zoonosis with medical importance because current treatment exhibits high toxicity and variable efficacy. To overcome these challenges, searching for bioactive molecules with new molecular targets is essential. Arginase enzyme has emerged as a significant therapeutic target against leishmaniasis due to its involvement in the synthesis of polyamines and trypanothione, vital molecules for parasite survival. Coordination phenolic compounds with transition metals offers potential to enhance biological activity by creating three-dimensional globular structures, the different possibilities of bonds and reactions in molecular targets, and physicochemical properties that can bring improved therapeutic efficacy. 

Objetivo (s)

This study aims to evaluate the in vitro inhibitory effect of catechin and quercetin coordinated by metal cupric cation (CC2 and QC2, respectively) on Leishmania infantum arginase (LiARG) and parasite viability. 

Material e Métodos

LiARG was expressed in Escherichia coli and purified by nickel affinity chromatography. The inhibitory activity of the metal compounds [100 µM] was assessed during LiARG reaction with L-arginine and quantified by urea dosage. Anti-L. infantum activity was tested in promastigotes treated for 48 h, and viability was determined with resazurin. From this, the 50% inhibitory concentration (IC50) was calculated by regression analysis of the dose-response curve. Similarly, the 50% cytotoxic concentration (CC50) was calculated after the MTT assay in host macrophages (RAW 264.7) treated for 48 h. 

Resultados e Conclusão

Therefore, CC2 and QC2 inhibited LiARG by 63.46 ± 3% and 80.26 ± 1.4%, respectively, surpassing catechin (C1, 45.6 ± 1.53%) and quercetin (Q1, 56.4 ± 2.7%). The copper coordination potentiated the anti-L. infantum activity, since C1 and Q1 not shown activity at 400 µM and the IC50 of CC2 was 29.9 ± 4.6 µM and QC2 was 23.8 ± 5.6 µM. Low cytotoxicity was observed with CC50 of 295.7 ± 21 µM for CC2 and 345.5 ± 30.5 µM for QC2, generating selectivity indices of 9.89 and 14.5, respectively. In conclusion, copper-coordinated phenolic compounds enhance arginase inhibition and L. infantum death with low cytotoxicity for host cells. Future steps involve assessing parasite load reduction in macrophages and understanding enzyme-ligand interactions.

Palavras Chave

Visceral Leishmaniasis; Zoonosis; enzymatic inhibition