| Grant number: | 24/15691-3 |
| Support Opportunities: | Scholarships in Brazil - Master |
| Start date: | December 01, 2024 |
| End date: | November 30, 2026 |
| Field of knowledge: | Biological Sciences - Parasitology - Protozoology of Parasites |
| Principal Investigator: | Juliana Quero Reimão Dalla Zanna |
| Grantee: | Gabriela Pereira dos Santos |
| Host Institution: | Faculdade de Medicina de Jundiaí (FMJ). Prefeitura Municipal de Jundiaí. Jundiaí , SP, Brazil |
| Associated research grant: | 18/18954-4 - Drug repurposing: evaluation of activity, selectivity and mechanism of action of new drug candidates against Toxoplasma gondii, AP.JP |
Abstract Introduction: Leishmaniasis and toxoplasmosis are globally prevalent parasitic diseases caused by Leishmania sp. and Toxoplasma gondii, respectively. The treatment of these diseases faces significant limitations, such as toxicity and the increasing reports of parasitic resistance, underscoring the need for the identification of new drugs with anti-Leishmania and anti-Toxoplasma activity. Aspartic protease inhibitors, originally developed as anti-HIV agents, are promising compounds for the treatment of various opportunistic infections, including toxoplasmosis and leishmaniasis. Objective: The aim of the present work is to investigate the anti-T. gondii and anti-Leishmania activity of aspartic protease inhibitors, as well as to select parasites that are tolerant or resistant to one of the compounds with selective antiparasitic activity. Method: An in vitro evaluation of aspartic protease inhibitors will be conducted against tachyzoites of the RH strain of T. gondii, promastigotes and amastigotes of Leishmania infantum, and human foreskin fibroblasts (HFF). The Effective Concentration 50% (EC50), Cytotoxic Concentration 50% (CC50), and Selectivity Index (SI) values of these compounds will be determined. Compounds with a high SI and desirable absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics will be selected. In addition, parasites that are tolerant or resistant to one of these compounds will be selected. Expected Results: This study is expected to contribute to the discovery of safer and more effective candidates against toxoplasmosis and leishmaniasis. | |
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