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Evaluation of synthetic selenium and telurium compounds as candidate drugs for treatment of Chagas Disease by a metabolomics approach

Grant number: 19/24107-5
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2020
Effective date (End): July 31, 2021
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
Principal Investigator:Marina Franco Maggi Tavares
Grantee:Ana Paula de Godoy Fernandes
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chagas disease is a neglected tropical disease, caused by Trypanosome parasites, affecting ca. 8 million people around the world. Despite the possibility of the disease's treatment, the existing therapeutic arsenal is still limited. The available drugs present high toxicity and several side effects have been reported. Still, the long duration of treatment associated with its high cost makes adherence very difficult. In this context, the search for new therapies has been encouraged. Selenium (Se) and tellurium (Te) compounds represent a chemical class with potential anti-parasitic action, although very few have been tested in vitro against the parasite Trypanosoma cruzi (T.cruzi). Metabolomics, which is a comparative analysis of altered metabolites in a biological system after an external intervention, has been used in therapeutic studies, such as for the discovery of new drugs and disease biomarkers. This project aims to apply a global metabolic approach, using GC-MS in the analysis of intracellular metabolites, to investigate in vitro the anti-trypanosome action of synthetic organic compounds of Se and Te. These compounds are selected from a chemical library, which contains 46 structures in total. A preliminary screening to verify the effectiveness of these compounds was performed, by cytotoxicity assays, showing that 8 of them have potential anti-trypanosome action. The screening work should be continued to select the 2 most promising compounds, one from each Se and Te compound series, which will be contrasted against the reference drug (Benznidazole, active principle of Rochagan, Roche). As a result, it is expected to understand the mechanisms of action of the compounds under investigation at the metabolic level and possibly contribute to the development of new drugs for treating Chagas disease. (AU)