Kinectic characterization and preliminary crystallization studies of Leishmania braziliensis trypanothione reductase

• Grant number: 18/24109-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2019
• End date: November 30, 2020
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Maria Cristina Nonato
• Grantee: Olívia Teixeira
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Leishmaniasis are a group of neglected diseases that puts 350 million individuals at risk. It is caused by parasites of the genus Leishmania and transmitted by the bite of infected femalephlebotomine sandflies. There are three main forms of the disease: cutaneous, mucocutaneous and visceral. The mucocutaneous form induces deformative lesions in the nasopharyngeal and oral mucosa that in Brazil is mainly caused by the parasite Leishmania braziliensis. The current treatment available for Leishmaniasis leads to side effects highly harmful to the patient's health leading to renal, cardiac and hepatic problems. They are costly, require long treatment regimes and are becoming more and more ineffective. They require a support infrastructure for exams and hospitalization, usually not available in endemic areas once the disease has a strong association with poverty. Parasites of the kinetoplast order which the genus Leishmania belongs have a distinct metabolic process of oxidative stress control compared with most eukaryotes. The main enzyme in kinetoplastida is trypanothione reductase (TR), while in eukaryotic processes is glutathione reductase (GR). The relevance to the parasite metabolism associated with structural differences between TR e human GR suggest TR as a potential therapeutic target for the development of new therapies with leishmanicidal activity. Within this context, the aim of the project is to perform the kinetic, biophysical characterization and crystallization as a first step to evaluate TR as a drug target against Leishmaniasis

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TEIXEIRA, OLIVIA; LACERDA, PEDRO; FROES, THAMIRES QUADROS; NONATO, MARIA CRISTINA; CASTILHO, MARCELO SANTOS. Druggable hot spots in trypanothione reductase: novel insights and opportunities for drug discovery revealed by DRUGpy. Journal of Computer-Aided Molecular Design, JUN 2021. (18/24109-5)

TEIXEIRA, OLIVIA; LACERDA, PEDRO; FROES, THAMIRES QUADROS; NONATO, MARIA CRISTINA; CASTILHO, MARCELO SANTOS. Druggable hot spots in trypanothione reductase: novel insights and opportunities for drug discovery revealed by DRUGpy. Journal of Computer-Aided Molecular Design, v. 35, n. 8, p. 871-882, AUG 2021. (18/24109-5)