Scholarship 22/16698-6 - Citotoxicidade, Doença de Chagas - BV FAPESP
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Investigation of the Activity of New Drug Candidates for Chagas Disease and Visceral Leishmaniasis

Grant number: 22/16698-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: August 01, 2023
End date until: July 31, 2024
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Adriano Defini Andricopulo
Grantee:Gustavo Augusto Vieira Macêdo
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Among the twenty Neglected Tropical Diseases (NTDs) described by the World Health Organization (WHO), Chagas disease and leishmaniasis stand out due to the high incidence of contagion and incapacitation. Present in tropical and subtropical regions associated with conditions of poverty, predominantly in Africa, Asia and the Americas, it is estimated that more than a 1 million individuals are affected by NTDs in 150 countries. Despite representing an important world public health problem, the development of new therapies to treat these diseases is still scarce, since investments in this area are insufficient. The available treatments are obsolete, have low efficacy and serious adverse effects, in addition to a concerning emergence of drug resistance. In this context, this research project aims to carry out biological screenings for the identification of new drug candidates for Chagas disease and leishmaniasis. Series of compounds will be evaluated in cellular assays against intracellular amastigotes of Trypanosoma cruzi and Leishmania infantum, which cause Chagas disease and leishmaniasis, respectively. The antiparasitic activities of these compounds will be identified in phenotypic assays and investigated through structure-activity relationship studies. The compounds will also be submitted to cytotoxicity assays in human fibroblasts (HFF-1), macrophages (THP-1) and hepatocytes (HepG2) strains. This project will enable the identification of effective, selective and safe drug candidates for the treatment of Chagas disease and visceral leishmaniasis. The work will be developed at the Laboratory of Medicinal and Computational Chemistry (LQMC) of the Institute of Physics of São Carlos (IFSC) of the University of São Paulo (USP).

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