Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 2nd floor, (C1113AAD), Buenos Aires, Argentina.
Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), CONICET - Universidad de Buenos Aires, Junín 956, 2nd floor, (C1113AAD), Buenos Aires, Argentina.
Nat Prod Res. 2024 Feb-Mar;38(4):690-695. doi: 10.1080/14786419.2023.2188208. Epub 2023 Mar 20.
Chagas disease is an infection caused by the protozoan affecting 6-8 million people worldwide. Only two drugs are available for its treatment, having a limited efficacy and adverse side-effects. Estafietin is a sesquiterpene lactone isolated from with activity against and low cytotoxicity against mammalian cells. The aim of this work was to predict the toxicologic profile of estafietin by methods and assess its activity on a murine model of Chagas disease. Estafietin showed low toxicity according to pkCSM web tool and passed the PAINS filter from PAINS-remover web server. The treatment of infected mice with 1 mg/Kg/day of estafietin for five consecutive days administrated by intraperitoneal route significatively decreased parasitemia levels and reduced inflammatory infiltrates and myocyte damage on muscle tissue. These results suggest that estafietin had effect both on acute and chronic stages of the infection.
恰加斯病是一种由原生动物引起的感染，影响全球 600 至 800 万人。目前仅有两种药物可用于治疗该病，但其疗效有限，且具有不良反应。埃斯塔菲汀是一种从分离得到的倍半萜内酯，具有抗活性和低细胞毒性。本研究旨在通过计算方法预测埃斯塔菲汀的毒理学特征，并评估其在恰加斯病小鼠模型中的活性。埃斯塔菲汀经 pkCSM 网络工具预测显示毒性低，且通过 PAINS-remover 网络服务器的 PAINS 过滤器。用 1mg/Kg/天的埃斯塔菲汀连续 5 天腹腔注射感染小鼠，可显著降低寄生虫血症水平，并减少肌肉组织中的炎症浸润和肌细胞损伤。这些结果表明，埃斯塔菲汀对感染的急性和慢性阶段均有作用。
