Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203, La Laguna, Tenerife, Islas Canarias, Spain; Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Tenerife, Islas Canarias, Spain.
Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Avda. Fco. Sánchez 3, 38206, La Laguna, Tenerife, Islas Canarias, Spain; Departamento de Química, Unidad Departamental de Química Analítica, Universidad de La Laguna (ULL), Tenerife, 38206, Spain.
Int J Parasitol Drugs Drug Resist. 2023 Aug;22:72-80. doi: 10.1016/j.ijpddr.2023.05.001. Epub 2023 May 31.
Chagas disease causes a problematic pathology that can lead to megacolon and heart disease, and can even cause the death of the patient. Current therapies for this disease are the same as they were 50 years ago, are not fully effective and have strong side effects. The lack of a safe and effective therapy makes it necessary to search for new, less toxic and totally effective compounds against this parasite. In this work, the antichagasic activity of 46 novel cyanomethyl vinyl ether derivatives was studied. In addition, to elucidate the type of cell death that these compounds produce in parasites, several events related to programmed cell death were studied. The results highlight four more selective compounds, E63, E64, E74 and E83, which also appear to trigger programmed cell death, and are therefore postulated as good candidates to use in future therapeutics for Chagas disease.
恰加斯病会导致严重的病理问题,可引发巨结肠和心脏病,甚至可能导致患者死亡。目前针对这种疾病的治疗方法与 50 年前相同,无法完全有效,且副作用较强。由于缺乏安全有效的治疗方法,因此有必要寻找针对这种寄生虫的新型、低毒且完全有效的化合物。在这项工作中,研究了 46 种新型氰甲基乙烯基醚衍生物的抗恰加斯病活性。此外,为了阐明这些化合物在寄生虫中产生的细胞死亡类型,研究了与程序性细胞死亡相关的几种事件。研究结果突出了四种更具选择性的化合物 E63、E64、E74 和 E83,它们似乎也能引发程序性细胞死亡,因此被推测为未来治疗恰加斯病的候选药物。