Therapeutic activity of organotin compounds against Trypanosoma cruzi

Abstract

An estimated 8 million people in Mexico, Central America, and South America are infected with Chagas disease (ChD) caused by the protozoan parasite Trypansoma cruzi (T. cruzi). ChD is a zoonotic disease transmitted to humans and animals by the insect vector Triatomine, also known as “kissing bug”. About 20 to 30% of infected people will develop symptomatic, potentially life‐threatening ChD. T. cruzi is carried in the hindgut of the triatomine bugs and transmission occurs when infected bug feces contact mucosal membranes or open wounds. Humans can also be infected through vector‐borne, blood‐borne, organ derived, congenital and oral transmission routes. Currently, ChD can be treated with Benznidazole and Nifurtiox. However, its efficacy is limited. In addition, the undesirable side effects of both drugs are a major drawback. Thus, the development of effective new chemotherapies against ChD is imperative. Previously, organotin compounds have shown to be broad and potent biocides against eukaryotic infections ranging from fungicides to acaricides. However, the use of these compounds against parasitic infections has not been investigated, possibly due to their immunotoxicity. Therefore, the aim of this study is to assess novel organotin compounds as anti‐Trypanosoma cruzi agents in an in vitro model of ChD. In this study, we tested the activity of a tetravalent organotin compound [MeS(CH2)3]2SnCl2 and compared it to commercially available organotin compounds such as Ph2SnCl2, (butyl)2SnCl2, and (octyl)2SnCl2. [MeS(CH2)3]2SnCl2. It is important to highlight that our novel compound acts as a benign organotin compound in respect to interactions with human natural killer cells. Therefore, we used the epimastigote forms of the transgenic strain of T. cruzi CL‐Brener expressing luciferase to test for parasitic viability; 2 × 106 parasites were incubated with the compounds in a range of 2 ‐ 0.625 mM for 72 hours at 28°C. Two controls were included in the assay, a negative control using only the drug diluent (1% DMSO) and a positive control where the parasites were treated with Benznidazole (80 mM). Following incubation, parasite viability was measured by the presence of luminescence after the addition of the luciferin substrate by ONE‐Gloä Luciferase Assay System (Promega). Treatment with compounds Ph2SnCl2 and (butyl)2SnCl2 resulted in an IC50 of 0.3 and 0.125 mM. Together, these preliminary results provide evidence that compounds Ph2SnCl2 and (butyl)2SnCl2 affect parasite viability. Thus, these findings can be further extended to investigate the tetravalent organotin compound [MeS(CH2)3]2SnCl2 therapeutic effects in the infective and intracellular stages of T. cruzi, and its potential cell cytotoxicity in human cells.Support or Funding InformationResearch reported in this poster was supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers RL5GM118969, TL4GM118971, and UL1GM118970. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.