1. Copaifera spp. oleoresins and two isolated compounds (ent-kaurenoic and ent-polyalthic acid) inhibit Toxoplasma gondii growth in vitro.
- Author
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Teixeira, Samuel Cota, de Souza, Guilherme, Junior, Joed Pires de Lima, Rosini, Alessandra Monteiro, Martínez, Aryani Felixa Fajardo, Fernandes, Thales Alves de Melo, Ambrósio, Sergio Ricardo, Veneziani, Rodrigo Cassio Sola, Bastos, Jairo Kenupp, Martins, Carlos Henrique Gomes, Barbosa, Bellisa Freitas, and Ferro, Eloisa Amália Vieira
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DITERPENES , *TOXOPLASMA gondii , *OLEORESINS , *HELA cells , *DIRECT action , *MOLECULAR docking , *CELL anatomy - Abstract
Toxoplasmosis affects about one-third of the world's population. The disease treatment methods pose several side effects and do not efficiently eliminate the parasite, making the search for new therapeutic approaches necessary. We aimed to assess the anti- Toxoplasma gondii activity of four Copaifera oleoresins (ORs) and two isolated diterpene acids, named ent -kaurenoic and ent -polyalthic acid. We used HeLa cells as an experimental model of toxoplasmosis. Uninfected and infected HeLa cells were submitted to the treatments, and the parasite intracellular proliferation, cytokine levels and ROS production were measured. Also, tachyzoites were pre-treated and the parasite invasion was determined. Finally, an in silico analysis was performed to identify potential parasite targets. Our data show that the non-cytotoxic concentrations of ORs and diterpene acids controlled the invasion and proliferation of T. gondii in HeLa cells, thus highlighting the possible direct action on parasites. In addition, some compounds tested controlled parasite proliferation in an irreversible manner. An additional and non-exclusive mechanism of action involves the modulation of host cell components, by affecting the upregulation of the IL-6. Additionally, molecular docking suggested that ent -polyalthic acid has a high affinity for the active site of the TgCDPK1 protein. Copaifera ORs have great antiparasitic activity against T. gondii , and this effect can be partially explained by the presence of the isolated compounds ent -kaurenoic and ent -polyalthic acid. [Display omitted] • Copaifera ORs and diterpenes acids decrease T. gondii intracellular proliferation in an irreversible manner. • Copaifera ORs and diterpenes acids up-regulate the IL-6 levels in Hela cells. • Ent-polyalthic acid promotes the reduction of ROS production in T. gondii -infected HeLa cells. • Molecular docking analysis indicated that Ent-polyalthic acid has high affinity for the active site of TgCDPK1. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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