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.

This is the first study to show the potential of IS in the control of Ae. aegypti. Further studies are needed to understand the mode of action of these compounds in the biological development of this mosquito species. © 2017 Society of Chemical Industry.

Herein, we report on the synthesis of imidazolium salt end-functionalized PLLA (PLLA-IS) and its application in the preparation of reduced graphene oxide–PLLA composites.

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