Selection of new drug candidates in Leishmaniasis

• Grant number: 18/22789-9
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2019
• Effective date (End): December 31, 2019
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: André Gustavo Tempone Cardoso
• Grantee: Marina Ferreira Camussi
• Home Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Visceral leishmaniasis is a neglected disease that mainly affects developing countries. Available chemotherapy for the treatment of leishmaniasis has a reduced number of drugs, with severe adverse effects and progressive increase of resistance. Drug repositioning consists in the search for new uses for approved drugs and is a great opportunity to introduce new therapies by significantly reducing the time and costs of the research. Antiarrhythmics are drugs used to control and prevent cardiac arrhythmias and have demonstrated efficacy both in vitro and in vivo against Leishmania spp. In this study, an in vitro screening of different commercial antiarrhythmic drugs will be carried out on intracellular amastigotes and promastigotes of Leishmania (L.) infantum. Additionally, a cytotoxicity study will be performed in mammalian cells to obtain the selectivity index. The most active drug will be studied for the mechanism of action, through evaluations of the integrity of the plasma membrane, as well as the evaluation of mitochondrial integrity. For this, different fluorescent probes will be used to evaluate the plasma membrane permeability (SytoxGreen), electric potential of the plasma membrane (bisoxonol) and mitochondrial potential (rhodamine 123). Thus, the present study aims to contribute to the selection of new drug candidates for future experimental preclinical studies in visceral leishmaniasis.