Departamento de Parasitología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 07738, Mexico.
Laboratorio de Biotecnología Farmacéutica, Centro de Biotecnología Genómica, Instituto Politécnico Nacional, Reynosa 88710, Mexico.
Molecules. 2024 Aug 10;29(16):3796. doi: 10.3390/molecules29163796.
American trypanosomiasis or Chagas disease, caused by (), affects approximately 6-7 million people worldwide. However, its pharmacological treatment causes several uncomfortable side effects, causing patients' treatment abandonment. Therefore, there is a need for new and better treatments. In this work, the molecular docking of nine hundred twenty-four FDA-approved drugs on three different sites of trypanothione reductase of (TR) was carried out to find potential trypanocidal agents. Finally, biological evaluations in vitro and in vivo were conducted with the selected FDA-approved drugs. Digoxin, alendronate, flucytosine, and dihydroergotamine showed better trypanocidal activity than the reference drugs benznidazole and nifurtimox in the in vitro evaluation against the trypomastigotes form. Further, these FDA-approved drugs were able to reduce 20-50% parasitemia in a short time in an in vivo model, although with less efficiency than benznidazole. Therefore, the results suggest a combined therapy of repurposed and canonical drugs against infection.
美国锥虫病或恰加斯病，由（）引起，影响全世界约 600 至 700 万人。然而，其药理学治疗会引起几种不适的副作用，导致患者放弃治疗。因此，需要新的和更好的治疗方法。在这项工作中，对（TR）的三个不同部位的九百二十四种 FDA 批准药物进行了分子对接，以寻找潜在的杀锥虫药物。最后，对选定的 FDA 批准药物进行了体外和体内的生物评价。地高辛、阿伦膦酸盐、氟胞嘧啶和二氢麦角胺在针对锥虫体形式的体外评价中显示出比参考药物苯并咪唑和硝呋替莫更好的杀锥虫活性。此外，这些 FDA 批准药物能够在体内模型中在短时间内减少 20-50%的寄生虫血症，尽管效率低于苯并咪唑。因此，结果表明针对（）感染的重新利用和规范药物的联合治疗。
