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Experimental and computational evaluation of drug candidates for Chagas Disease and Visceral Leishmaniasis

Grant number: 23/14195-0
Support Opportunities:Scholarships in Brazil - Program to Stimulate Scientific Vocations
Effective date (Start): January 08, 2024
Effective date (End): February 27, 2024
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Adriano Defini Andricopulo
Grantee:Eliza Lima dos Santos
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Among the 20 Neglected Tropical Diseases (NTDs) mentioned by the World Health Organization (WHO), Chagas disease and leishmaniasis stand out for their high incidences of contagion and the high number of social disabilities. Presented in tropical and subtropical regions related to poverty conditions, predominantly in Africa, Asia and the Americas, it is estimated that 1.7 million individuals, per year, are targets of treatment and prevention strategies. Despite presenting an important public health problem, the development of new therapies to treat these diseases is still scarce, as investment funds in this area are limited. Furthermore, the treatments currently used are obsolete, are not fully effective, exhibit significant adverse effects and over time some strains develop resistance to drugs. In this context, the research project aims to carry out screening and identification of new molecules with antiparasitic potential. In this way, a series of compounds will be evaluated through cellular assays, seeking to identify and characterize the biological properties against the intracellular amastigote forms of T. cruzi and L. infantum, which will be expressed through IC50 values. The compounds will also be subjected to cytotoxicity tests, which will be evaluated for CC50 values, using fibroblast (HFF-1), macrophage (THP-1) and hepatocyte (HepG2) cell lines. Therefore, the research carried out will enable the selection of desired, more effective, selective and safe candidates for the treatment of Chagas disease and leishmaniasis. The proposed work will be developed at the Medicinal and Computational Chemistry Laboratory (LQMC) of the São Carlos Physics Institute (IFSC) of the University of São Paulo (USP). (AU)

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