Journal Article

Prenylated chalcone analog-mediated Inhibition of Toxoplasma gondii growth in human trophoblast cell line and villous explants

Almeida, Marcos Paulo Oliveira, Barbosa, Matheus Carvalho, Faria, Guilherme Vieira, Luz, Luana Carvalho, Oliveira, Rafael Martins, Regasini, Luis Octavio, de Souza, Guilherme, Santos, Natalia Carine Lima, Alves, Rosiane Nascimento, Rosini, Alessandra Monteiro, Oliveira Gomes, Angelica, Sousa, Daniel Pereira, Soares, Otavio Henrique Locateli, De Lima Júnior, Joed Pires, Barbosa, Bellisa Freitas, Fernandes, Thales Alves de Melo, Júnior, Vilson Serafim, Damasceno, Izadora Santos, Vieira Ferro, Eloisa Amália, Teixeira, Samuel Cota, Paschoalino, Marina

2025

Overview

Congenital toxoplasmosis is a significant public health issue caused by the transplacental passage of Toxoplasma gondii to the embryo/fetus. The standard treatment involves a combination of sulfadiazine and pyrimethamine, drugs often associated with adverse effects and high toxicity. The current study aimed to investigate the potential of prenylated chalcones (C2, C4 and C9) in controlling T. gondii infection in human trophoblast cells (BeWo) and human placental explants. As results, non-cytotoxic doses of C2, C4 and C9 impaired parasite invasion and subsequent intracellular proliferation in BeWo cells. Scanning and transmission electron microscopies evidenced the direct effect of chalcones on tachyzoites, which presented irregular rough surface, membrane with hole-like structures, torsion and shape substantial changes after pretreatment. C4 and, especially C9, caused notable ultrastructural damages due to the formation of vacuole-like structures in the parasite cytoplasm and surrounding the parasitophorous vacuole. Additionally, chalcones modulated the cytokine profile by increasing IL-8 and downmodulating MIF and ROS levels in BeWo cells and downregulating TNF-α release in villous explants. These findings highlight C2, C4, and C9 as promising candidates for the development of alternative therapies to prevent congenital toxoplasmosis, as well as chalcones as a valuable scaffold for the design of new anti- T. gondii agents.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/326/417 / 692/699 / Cell Line / Cell proliferation / Chalcones / Chalcones - chemistry / Chalcones - pharmacology / Cytoplasm / Cytotoxicity / Drug resistance / Enzymes / Explants / Female / Fetuses / Fibroblasts / Flavonoid / Humanities and Social Sciences / Humans / Infections / multidisciplinary / Original Research / originalresearch / Parasites / Parasitophorous vacuole / Placenta / Pregnancy / Protozoa / Public health / Pyrimethamine / Reactive Oxygen Species - metabolism / Science / Science (multidisciplinary) / Sulfadiazine / Tachyzoites / Toxicity / Toxoplasma - drug effects / Toxoplasma - growth & development / Toxoplasma - ultrastructure / Toxoplasma gondii / Toxoplasmosis / Toxoplasmosis - drug therapy / Toxoplasmosis - parasitology / Treatment / Trophoblast / Trophoblasts - drug effects / Trophoblasts - metabolism / Trophoblasts - parasitology / Tumor necrosis factor-α