Trypanosoma cruzi nitroreductase: search for new substrates and kinetic characterization

• Grant number: 16/26196-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2017
• End date: November 30, 2020
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Maria Cristina Nonato
• Grantee: Pedro Henrique Luccas
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The cause of Chagas disease is the parasite Trypanosoma cruzi that affects about 6 million to 7 million people worldwide, mostly in Latin America. Despite thousands of deaths and severely affecting the quality of life of infected patients, Chagas disease is still considered neglected by public and private health systems. Previously, Chagas disease was restrict to low-income population from emerging countries and tropical weather. Nowadays, due to globalization and human mobility, cases of Chagas disease are also reported for wealth regions of the world including United States and European countries. In Brazil, the only form of treatment is the Benznidazol, a pro-drug with limited efficacy and highly toxic, which is activated by the reduction of the nitro group by the enzyme nitroredutcase (TcNTR). Due to limited information regarding the mechanism of catalysis adopted by TcNTR and the urgent need for new therapeutic strategies to combat Chagas diseases, the present project focus the identification of new nitroheterocyclic compounds as TcNTR substrates, the characterization of its kinetic mechanism and the comparison of efficacy of related compounds front to the single-line treatment, the benznidazol. Our results will explore TcNTR as a therapeutic target for the development of new molecules with tripanocidal activity. (AU)