Moreno-Viguri Elsa, Jiménez-Montes Carmen, Martín-Escolano Rubén, Santivañez-Veliz Mery, Martin-Montes Alvaro, Azqueta Amaya, Jimenez-Lopez Marina, Zamora Ledesma Salvador, Cirauqui Nuria, López de Ceráin Adela, Marín Clotilde, Sánchez-Moreno Manuel, Pérez-Silanes Silvia
Department of Organic and Pharmaceutical Chemistry, Institute of Tropical Health, Universidad de Navarra , Pamplona 31008, Spain.
Departamento de Parasitología, Instituto de Investigación Biosanitaria (ibs.GRANADA), Hospitales Universitarios de Granada/Universidad de Granada , Granada 18014, Spain.
J Med Chem. 2016 Dec 22;59(24):10929-10945. doi: 10.1021/acs.jmedchem.6b00784. Epub 2016 Dec 6.
Chagas disease is a neglected tropical disease with 6-7 million people infected worldwide, and there is no effective treatment. Therefore, there is an urgent need to continue researching in order to discover novel therapeutic alternatives. We present a series of arylaminoketone derivatives as means of identifying new drugs to treat Chagas disease in the acute phase with greater activity, less toxicity, and a larger spectrum of action than that corresponding to the reference drug benznidazole. Indexes of high selectivity found in vitro formed the basis for later in vivo assays in BALB/c mice. Murine model results show that compounds 3, 4, 7, and 10 induced a remarkable decrease in parasitemia levels in acute phase and the parasitemia reactivation following immunosuppression, and curative rates were higher than with benznidazole. These high antiparasitic activities encourage us to propose these compounds as promising molecules for developing an easy to synthesize anti-Chagas agent.
恰加斯病是一种被忽视的热带疾病，全球有600 - 700万人感染，且尚无有效治疗方法。因此，迫切需要继续开展研究以发现新的治疗方案。我们展示了一系列芳基氨基酮衍生物，作为鉴定治疗急性期恰加斯病新药的手段，这些新药比参比药物苯硝唑具有更高的活性、更低的毒性和更广的作用谱。体外发现的高选择性指标为后续在BALB/c小鼠体内进行的试验奠定了基础。小鼠模型结果表明，化合物3、4、7和10可使急性期的寄生虫血症水平以及免疫抑制后的寄生虫血症再激活显著降低，治愈率高于苯硝唑。这些高抗寄生虫活性促使我们提出将这些化合物作为开发易于合成的抗恰加斯病药物的有前景分子。
