Imidazolium salts as innovative agents against Leishmania amazonensis

Abstract

The available chemotherapeutic drugs for the treatment of leishmaniasis present problems relating to efficacy, emergence of parasite resistance, and adverse effects and cost. Azole antifungal drugs have been repurposed for this proposition but the clinical response has been variable. In this sense, this study assessed the leishmanicidal and immunomodulatory activities of azoles-derived imidazolium salts (IS), being the ionic imidazole-derived equivalents: 1-n-butyl-3-methylimidazolium chloride (CMImCl), 1-n-decyl-3-methylimidazolium chloride (CMImCl), 1-n-hexadecyl-3-methylimidazolium chloride (CMImCl), 1-n-hexadecyl-3-methylimidazolium methanesulfonate (CMImMeS), 1-n-hexadecyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (CMImNTf) and 1-methyl-3-n-octadecylimidazolium chloride (CMImCl). Promastigotes of Leishmania amazonensis were incubated with IS at concentrations ranging from 0.1 to 100 μM, and the parasite survival was monitored. The effects of IS on reactive oxygen species (ROS) production and mitochondrial membrane potential of promastigotes, as well as on cytotoxicity against peripheral blood mononuclear cells (PBMC) and human erythrocytes were determined. Besides, the activities of IS against amastigotes and nitric oxide production were also evaluated. The IS inhibited parasite growth and showed potent leishmanicidal activity against promastigotes of L. amazonensis. In addition, IS induced mitochondrial dysfunction and ROS production in parasites, and presented low cytotoxicity against PBMC and human erythrocytes. Furthermore, at very low concentration (0.5 μM), CMImCl, CMImMeS, CMImCl, CMImCl and CMImNTf were able to kill intramacrophage parasites at levels of 91.3, 100, 94.4, 95.3 and 35.6%, respectively. These results indicate that IS are promising candidates for the development of drugs against L. amazonensis.

Imidazolium salts as alternative compounds to control diseases caused by plant pathogenic bacteria

“…This strengthens the importance of the relation between the N ‐alkyl chain length and the amphiphilic character in the biological activity of these salts (Zhao et al ). The results of this work correspond with those obtained not only for other Gram‐positive and Gram‐negative bacteria (Łuczak et al ), but also for other phylogenetically diverse parasites, such as the intracellular protozoan Leishmania amazonensis (Martins et al ), in which a correlation of the N‐ alkyl chain length and the inbition strenght was also observed. Altogether, this is in agreement with the structural resemblance between imidazolium salts with an optimized N ‐alkyl chain length and the hydrophobic moiety of membrane lipids.…”

“…They are derivatives of the imidazolium cation and an inorganic or organic anion (Riduan and Zhang ). In medicine and human health, imidazolium salts have been tested for a wide range of applications, such as antifungal (Schrekker et al ), fungal antibiofilm (Raucci et al ), antibacterial (Czekański et al ; Doria et al ), antiparasitic (Martins et al ) and larvicidal (Goellner et al ) agents. With regard to the potential use of imidazolium salts in agriculture, so far, only the results of a single study have been reported.…”

Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach

“…The first two ranked compounds, corosolic acid (1) and jacoumaric acid (2) were more active than guajadial B (5) and medicagenic acid (6), with an IC 50 of 1.32 ± 0.59 µg/mL for jacoumaric acid and 1.01 ± 0.06 µg/mL for corosolic acid ( Table 2). Since most antileishmanial drugs act by the production of reactive oxygen species (ROS) that lead to the death of parasites [23,24], we measured the production of ROS induced by jacoumaric acid and corosolic acid at the IC 50 (1.32 µg/mL and 1.06 µg/mL, respectively) and IC 90 (1.90 µg/mL and 1.43 µg/mL, respectively) using H 2 DCFDA (2 ,7 -dichlorodihydrofluorescein diacetate). The corresponding graph presented in Figure 4A clearly demonstrates that jacoumaric acid and corosolic acid have an antioxidant capacity, since the fluorescence proportional to the production of ROS significantly decreased compared to the control by addition of either compound regardless of the concentration used.…”

Investigating the Biological Activity of Imidazolium Aurate Salts

“…It should be mentioned that the IC 50 of compounds 6–8 exhibited much higher IC 50 than that of pentamidine, highlighting that highly hindered ortho ‐substituents on the N ‐aromatic ring of the imidazolium moiety were also detrimental for the antileishmanial activity. When compared to the imidazolium salts evaluated in the study of Romão, Schrekker and co‐workers where long linear aliphatic chains as N ‐substituents were evaluated, the herein reported compounds are less efficient in this application. Indeed, the anitleishmanial activity of the aliphatic imidazolium salts reported in the literature were found more active than amphotericin B, whereas the IC 50 values of imidazolium aurates 1–3 , 5 and 9 were all found slightly higher than that of this reference control (Table and Figure ).…”