Paschoalino Marina, Júnior Vilson Serafim, Soares Otavio Henrique Locateli, Luz Luana Carvalho, de Souza Guilherme, Rosini Alessandra Monteiro, Almeida Marcos Paulo Oliveira, Sousa Daniel Pereira, De Lima Júnior Joed Pires, Santos Natalia Carine Lima, Oliveira Rafael Martins, Damasceno Izadora Santos, Faria Guilherme Vieira, Barbosa Matheus Carvalho, Fernandes Thales Alves de Melo, Alves Rosiane Nascimento, Oliveira Gomes Angelica, Vieira Ferro Eloisa Amália, Teixeira Samuel Cota, Regasini Luis Octavio, Barbosa Bellisa Freitas
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberlândia, Campus Umuarama, Av. Pará, 1720, Uberlândia, MG, 38405320, Brazil.
Laboratory of Antibiotics and Chemotherapeutics, Institute of Bioscience, Human and Exact Sciences, Universidade Estadual Paulista, São José do Rio Preto, SP, Brazil.
Sci Rep. 2025 Jul 2;15(1):23539. doi: 10.1038/s41598-025-08764-y.
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.
先天性弓形虫病是由弓形虫经胎盘传播给胚胎/胎儿引起的一个重大公共卫生问题。标准治疗方法是联合使用磺胺嘧啶和乙胺嘧啶，这两种药物常伴有不良反应且毒性较高。本研究旨在探讨异戊烯基查耳酮（C2、C4和C9）在控制人滋养层细胞（BeWo）和人胎盘外植体中弓形虫感染方面的潜力。结果显示，C2、C4和C9的无细胞毒性剂量可损害BeWo细胞中寄生虫的入侵及随后的细胞内增殖。扫描电子显微镜和透射电子显微镜证明了查耳酮对速殖子的直接作用，速殖子在预处理后表面粗糙不规则、膜上出现孔状结构、扭曲且形状发生显著变化。C4，尤其是C9，由于在寄生虫细胞质中以及围绕寄生泡形成类空泡结构而导致明显的超微结构损伤。此外，查耳酮通过增加BeWo细胞中的IL-8并下调MIF和ROS水平以及下调绒毛外植体中的TNF-α释放来调节细胞因子谱。这些发现突出了C2、C4和C9作为预防先天性弓形虫病替代疗法的有前景的候选药物，以及查耳酮作为设计新型抗弓形虫药物的有价值的骨架。
