Centre for Parasitology and Mycology, Instituto Adolfo Lutz, São Paulo, SP, 01246-000, Brazil.
Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, SP, 09210-180, Brazil.
Acta Trop. 2021 Feb;214:105768. doi: 10.1016/j.actatropica.2020.105768. Epub 2020 Nov 25.
Considering the lack of effective and safe therapy for the treatment of Chagas disease, the antihypertensive drug manidipine (MDP) was in vitro evaluated against Trypanosoma cruzi. The bioenergetics of trypomastigotes was studied in the presence of the drug using fluorimetric and luminescent assays. Manidipine showed a potent antiparasitic activity, with IC values of 0.1 μM (intracellular amastigotes) and 3 μM (trypomastigotes), resulting in a promising selectivity index against the amastigotes (>1459). Using fluorimetric analysis, the drug showed depolarisation of the electric potential of the plasma membrane with no alteration of the permeability. A decrease in ATP levels suggested a bioenergetic alteration of the mitochondria, which was confirmed by the depolarisation of the mitochondrial membrane potential and a slight increase of the ROS levels. This is the first study to show the promising in vitro effectiveness of the antihypertensive MDP against T. cruzi, which may represent a candidate for future investigations in animal models.
鉴于目前缺乏有效且安全的药物来治疗恰加斯病，本研究采用荧光和发光检测方法，评估了抗高血压药物马尼地平（MDP）对克氏锥虫的体外抗虫活性。研究发现，MDP 对滋养体（IC 50 为 0.1 μM）和游离鞭毛体（IC 50 为 3 μM）均具有较强的抑制活性，其对滋养体的选择性指数（>1459）具有很大的应用潜力。荧光分析结果显示，MDP 能使质膜去极化而不改变其通透性。此外，MDP 还能降低 ATP 水平，提示线粒体的生物能量发生改变，这一结果也得到了线粒体膜电位去极化和 ROS 水平轻微升高的证实。本研究首次报道了抗高血压药物 MDP 对 T. cruzi 具有良好的体外抗虫效果，这为进一步在动物模型中开展相关研究提供了新的候选药物。
