Drug repurposing: evaluation of activity, selectivity and mechanism of action of new drug candidates against Toxoplasma gondii

• Grant number: 18/18954-4
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: October 01, 2020
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Juliana Quero Reimão Dalla Zanna
• Grantee: Juliana Quero Reimão Dalla Zanna
• Host Institution: Faculdade de Medicina de Jundiaí (FMJ). Prefeitura Municipal de Jundiaí. Jundiaí , SP, Brazil
• Associated researchers: Adriano Cappellazzo Coelho ; André Gustavo Tempone Cardoso ; Andrés Jimenez Galisteo Jr
• Associated research grant(s): 20/03399-5 - Multi-User Equipment approved in grant 2018/18954-4: microplate fluorometer and Luminometer, AP.EMU
• Associated scholarship(s): 24/22547-6 - Investigation of Thiazole Derivatives and Other Promising Compounds with Anti-Toxoplasma gondii Potential in Murine Models of Toxoplasmosis, BP.DR; 24/15691-3 - Evaluation of anti-Toxoplasma gondii and anti-Leishmania activity of aspartic protease inhibitors, BP.MS; 24/10179-2 - Assessment of activity and mechanism of action of synthetic compounds against Toxoplasma gondii, BP.MS; 23/18327-8 - In silico screening and in vitro investigation of the mechanism of action of candidates for cerebral toxoplasmosis therapy, BP.PD

Abstract

Toxoplasma gondii infects animals and humans, with about 30% of world population carrying the parasite, mostly in its latent form. T. gondii is a common cause of serious congenital infections, resulting in both severe fetal disease and subsequent illnesses in children and adults. Toxoplasmosis also causes serious illnesses in immunocompromised individuals, including encephalitis, chorioretinitis, pneumonitis, and myocarditis. For the drugs currently used to treat toxoplasmosis, long courses of therapy are required, and their use is often limited by side effects. Importantly, there is no available drug with efficacy against the bradyzoite stage of the parasite, which forms tissue cysts in deep organs, such as the brain, and can reactivate years after initial infection. Since the current therapeutic drugs for toxoplasmosis present serious host toxicity, research on effective substances of relatively low toxicity is urgently needed. To support this effort, the present project aims to evaluate the activity, efficacy, toxicity and mechanism of action of synthetic and natural compounds, in order to collaborate in the development of new therapeutic options for toxoplasmosis. From the data generated in this project, we intend to propose a new drug candidate for the treatment of toxoplasmosis. Considering that the proposed drugs have a well-established clinical safety, it is possible that the data obtained in this project may serve as the basis for a clinical pilot study. It is also intended to characterize the activity of synthetic and natural compounds against T. gondii by investigating its mechanism of action and potentially increasing knowledge about the parasite. (AU)

Scientific publications

(5)

(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)

REIMAO, JULIANA Q.; PEDRO, DEBORA P. PITA; COELHO, ADRIANO C.. The preclinical discovery and development of oral miltefosine for the treatment of visceral leishmaniasis: a case history. EXPERT OPINION ON DRUG DISCOVERY, v. 15, n. 6, MAR 2020. (18/18954-4, 16/21171-6)

CAJAZEIRO, DEBORA CHAVES; TOLEDO, PAULA PEREIRA MARQUES; DE SOUSA, NATALIA FERREIRA; SCOTTI, MARCUS TULLIUS; REIMAO, JULIANA QUERO. Drug Repurposing Based on Protozoan Proteome: In Vitro Evaluation of In Silico Screened Compounds against Toxoplasma gondii. PHARMACEUTICS, v. 14, n. 8, p. 15-pg., 2022-08-01. (18/18954-4, 20/03399-5)

DOS SANTOS, GABRIELA P.; COELHO, ADRIANO C.; REIMAO, JULIANA Q.. The latest progress in assay development in leishmaniasis drug discovery: a review of the available papers on PubMed from the past year. EXPERT OPINION ON DRUG DISCOVERY, v. 20, n. 2, p. 16-pg., 2025-01-10. (20/03399-5, 24/15691-3, 18/18954-4)

DOS SANTOS, BRUNA RAMOS; RAMOS, AMANDA BRUNO DA SILVA BELLINI; DE MENEZES, RENATA PRISCILA BARROS; SCOTTI, MARCUS TULLIUS; COLOMBO, FABIO ANTONIO; MARQUES, MARCOS JOSE; REIMAO, JULIANA QUERO. Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice. PLoS One, v. 18, n. 7, p. 16-pg., 2023-07-07. (18/18954-4, 20/03399-5)

REIMAO, JULIANA QUERO; COSER, ELIZABETH MAGIOLO; LEE, MONICA RAN; COELHO, ADRIANO CAPPELLAZZO. Laboratory Diagnosis of Cutaneous and Visceral Leishmaniasis: Current and Future Methods. MICROORGANISMS, v. 8, n. 11, NOV 2020. (16/21171-6, 18/18954-4)