In vivo experiments demonstrate the potent antileishmanial efficacy of repurposed suramin in visceral leishmaniasis

Abstract

Background Treatment failure and resistance to the commonly used drugsremains a major obstacle for successful chemotherapy against visceral leishmaniasis (VL). Since the development of novel therapeutics involves exorbitant costs, the effectiveness of the currently available antitrypanosomatid drug suramin has been investigated as an antileishmanial, specifically for VL,in vitro and in animal model experiments. Methodology/Principal Leishmaniadonovanipromastigotes were treated with suramin and studieswere performed to determine the extent and mode of cell mortality, cell cycle arrest and other invitroparameters. In addition, L. donovani infected BALB/c mice were administered suramin and a host of immunological parameters determined to estimate the antileishmanial potency of the drug. Finally, isothermal titration calorimetry (ITC)and enzymatic assays were used to probe the interaction of the drug with one of its putative targets namely parasitic phosphoglycerate kinase (LmPGK). Findings The in vitro studiesrevealed the potential efficacy of suramin against theLeishmaniaparasite. This observation was further substantiated in the in vivomurine model, which demonstrated thatupon suramin administration, the Leishmania infected BALB/c mice were able to reduce the parasitic burden and alsogenerate the host protective immunological responses. ITC and enzyme assays confirmed the binding and consequent inhibition of LmPGK due to the drug. Conclusions/Significance Allexperiments affirmed the efficacy ofsuramin againstL. donovani infection, which could possibly lead to its inclusion in the repertoire of drugs against VL.