Department of Parasitology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China.
College of Chemistry, Sichuan University, Chengdu, Sichuan, China.
Acta Trop. 2023 Jan;237:106741. doi: 10.1016/j.actatropica.2022.106741. Epub 2022 Nov 2.
Currently, symptomatic toxoplasmosis is treated with a combination of sulfadiazine and pyrimethamine. However, significant adverse effects and drug resistance have been reported. Terpenoids are widely found in nature, with numerous studies demonstrating that they have effective inhibitory effects on a variety of parasites.
In this study, we employed intermediates or derivatives of lindenane sesquiterpenoids to evaluate their intracellular and extracellular inhibitory effects on Toxoplasma gondii tachyzoites and their cytotoxicity on macrophages.
We demonstrated that two of these target terpenoids could effectively reduce the number of extracellular tachyzoites, probably by inducing tachyzoite apoptosis through altering tachyzoites mitochondrial membrane potential and calcium homeostasis. In addition, the two target terpenoids were able to promote intracellular tachyzoites elimination, possibly by enhancing macrophage activities.
Two derivatives of lindenane sesquiterpenoids with low cytotoxicity to macrophages demonstrated direct and indirect antitoxoplasma effects.
目前，针对有症状的弓形体病采用磺胺嘧啶和乙胺嘧啶联合治疗。然而，已有报道称该治疗方案存在严重的不良反应和耐药性。萜类化合物在自然界中广泛存在，大量研究表明其对多种寄生虫具有有效的抑制作用。
本研究采用丁香烷倍半萜类化合物的中间体或衍生物来评估它们对刚地弓形虫速殖子的细胞内和细胞外抑制作用及其对巨噬细胞的细胞毒性。
我们证明了这两种目标萜类化合物可以有效地减少细胞外速殖子的数量，可能是通过改变速殖子的线粒体膜电位和钙稳态来诱导速殖子凋亡。此外，这两种目标萜类化合物还能够促进细胞内速殖子的清除，可能是通过增强巨噬细胞的活性。
两种对巨噬细胞低细胞毒性的丁香烷倍半萜类衍生物具有直接和间接的抗弓形虫作用。
