Núcleo de Pesquisa Em Doenças Negligenciadas, Universidade Guarulhos, R. Eng. Prestes Maia, 88, Centro, Guarulhos, SP, 07023-070, Brazil.
Laboratório de Imunopatologia da Esquistossomose (LIM-06), Departamento de Moléstias Infecciosas E Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Parasitol Res. 2021 Nov;120(11):3837-3844. doi: 10.1007/s00436-021-07333-2. Epub 2021 Oct 4.
Schistosomiasis is a major public health problem that afflicts more than 240 million individuals globally, particularly in poor communities. Treatment of schistosomiasis relies heavily on a single oral drug, praziquantel, and there is interest in the search for new antischistosomal drugs. This study reports the anthelmintic evaluation of carvacryl acetate, a derivative of the terpene carvacrol, against Schistosoma mansoni ex vivo and in a schistosomiasis animal model harboring either adult (patent infection) or juvenile (prepatent infection) parasites. For comparison, data obtained with gold standard antischistosomal drug praziquantel are also presented. Initially in vitro effective concentrations of 50% (EC) and 90% (EC) were determined against larval and adult stages of S. mansoni. In an animal with patent infection, a single oral dose of carvacryl acetate (100, 200, or 400 mg/kg) caused a significant reduction in worm burden (30-40%). S. mansoni egg production, a process responsible for both life cycle and pathogenesis, was also markedly reduced (70-80%). Similar to praziquantel, carvacryl acetate 400 mg/kg had low efficacy in pre-patent infection. In tandem, although carvacryl acetate had interesting in vitro schistosomicidal activity, the compound exhibited low efficacy in terms of reduction of worm load in S. mansoni-infected mice.
血吸虫病是一种严重的公共卫生问题,影响着全球超过 2.4 亿人,尤其是贫困社区的人群。血吸虫病的治疗主要依赖于一种单一的口服药物——吡喹酮,因此人们对寻找新的抗血吸虫药物很感兴趣。本研究报告了萜烯香芹酚的衍生物——乙酸香芹酯在体外和携带成虫(现症感染)或幼虫(潜在感染)寄生虫的血吸虫病动物模型中的驱虫评估。为了进行比较,还提供了金标准抗血吸虫药物吡喹酮的数据。最初,针对曼氏血吸虫的幼虫和成虫阶段,确定了乙酸香芹酯的 50%(EC)和 90%(EC)有效浓度。在现症感染的动物中,单次口服乙酸香芹酯(100、200 或 400mg/kg)可显著降低虫体负荷(30-40%)。曼氏血吸虫的产卵量(负责生命周期和发病机制的过程)也明显减少(70-80%)。与吡喹酮相似,乙酸香芹酯 400mg/kg 在潜在感染中疗效较低。虽然乙酸香芹酯在体外具有有趣的杀血吸虫活性,但该化合物在降低曼氏血吸虫感染小鼠的虫体负荷方面的疗效较低。