Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA
Programa de Doctorado en Ciencias en Biotecnología, Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Obregon City, Sonora, Mexico.
Antimicrob Agents Chemother. 2020 Apr 21;64(5). doi: 10.1128/AAC.02233-19.
is an under-reported, pathogenic free-living amoeba that causes amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and 10 μM, we identified 54 hits that significantly inhibited the growth of Hits were reconfirmed in quantitative dose-response assays and 23 compounds (42.6%) were confirmed with activity greater than miltefosine, the current standard of care.
是一种报道较少的致病性自由生活阿米巴原虫，可引起阿米巴性脑炎（BAE）和皮肤皮肤感染。虽然皮肤感染通常不会致命，但伴有或不伴有皮肤受累的 BAE 通常是致命的。这是由于缺乏既有效又能穿过血脑屏障的药物。我们旨在通过筛选开源的疟疾药物 Venture（MMV）疟疾框和 MMV 病原体框来发现新药发现的新线索，总共 800 种化合物。从初始的 1 和 10μM 单点筛选中，我们确定了 54 个显著抑制生长的命中物。在定量剂量反应测定中重新确认了命中物，并且 23 种化合物（42.6％）的活性大于米替福新，米替福新是当前的护理标准。
