Banca de DEFESA: DARLY DA SILVA FERREIRA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : DARLY DA SILVA FERREIRA
DATE: 15/10/2026
TIME: 09:30
LOCAL: Mista, Videoconferência e auditório na SEDIS
TITLE:

Activity of Endoperoxide-Derived Compounds and a Morita–Baylis–Hillman Adduct Using an Experimental Model of Toxoplasma gondii

KEY WORDS:

Antiparasitic; Toxoplasmosis; Trioxolanes; Tetraoxanes; Isatin; Medicinal chemistry.

PAGES: 72
BIG AREA: Ciências Biológicas
AREA: Parasitologia
SUMMARY:

Toxoplasma gondii, the etiological agent of toxoplasmosis, is an obligate intracellular parasite with a cosmopolitan distribution, capable of infecting various mammalian and avian species, including humans. Controlling the infection remains a challenge, primarily due to the limited availability of therapeutic options. This issue is particularly relevant in Brazil, where the high genetic diversity of T. gondii includes non-archetypal strains associated with increased virulence, atypical clinical manifestations, and reduced susceptibility to conventional treatments. In this context, the need to identify new compounds with antiparasitic activity is underscored, highlighting the exploration of pharmacophores for the synthesis of novel endoperoxides, as well as the application of medicinal chemistry based on the Morita–Baylis–Hillman reaction. Thus, this study aimed to evaluate the anti-T. gondii activity of endoperoxide-derived compounds and an AMBH derivative using in vitro and in vivo experimental models. For the in vitro assays, NHDF cell monolayers were infected with 1x10³ tachyzoites of the RH strain and treated with the compounds at a concentrations of 0,41, 0,81, 1,62, 3,25 e 6,5 µg/mL, using pyrimethamine (1 µM) as the reference drug and DMSO (0.1%) as the control. After seven days of treatment, the cells were fixed, stained with crystal violet, and analyzed using an image acquisition system. In the in vivo assays, BALB/c mice were treated daily with the compounds for five days and, one hour after the initial treatment, infected via gavage with 25 tissue cysts of the T. gondii ME49 strain; the animals were monitored for 20 days. Sulfadiazine was used in parallel as the reference drug. In vitro results demonstrated that the endoperoxide compounds were capable of inhibiting tachyzoite replication by up to 100%, in addition to inducing alterations in cellular architecture and the appearance of lipid granules. In in vivo assays, the endoperoxide compounds IC71 and IC83, as well as AMBH, reduced the tissue cyst burden in the animals brains. Taken together, the results highlight the antiparasitic potential of the evaluated molecules and underscore the importance of identifying new therapeutic candidates against T. gondii. Future studies may investigate the most promising compounds against virulent, non-archetypal T. gondii genotypes isolated in Rio Grande do Norte.

COMMITTEE MEMBERS:
Externa à Instituição - MARIA REGINA REIS AMENDOEIRA - Fiocruz - RJ
Externa à Instituição - MARIA DE LURDES DOS SANTOS CRISTIANO
Presidente - 2213126 - VALTER FERREIRA DE ANDRADE NETO