PDF(Pubmed)
Abstract：
Primary amoebic meningoencephalitis (PAM) is a rare and fulminant neurodegenerative disease caused by the free-living amoeba Naegleria fowleri. Currently, there is a lack of standardized protocols for therapeutic action. In response to the critical need for effective therapeutic agents, we explored the Global Health Priority Box, a collection of 240 compounds provided by the Medicines for Malaria Venture (MMV). From this pool, flucofuron emerged as a promising candidate, exhibiting high efficacy against trophozoites of both N. fowleri strains (ATCC 30808 IC50 : 2.58 ± 0.64 μM and ATCC 30215 IC50: 2.47 ± 0.38 μM), being even active against the resistant cyst stage (IC50: 0.88 ± 0.07 μM). Moreover, flucofuron induced diverse metabolic events that suggest the triggering of apoptotic cell death. This study highlights the potential of repurposing medications for treating challenging diseases, such as PAM.
摘要：
原发性阿米巴脑膜脑炎（PAM）是一种罕见的暴发性神经退行性疾病，由自由生活的阿米巴Naegleriafowleri引起。目前,缺乏标准化的治疗方案.为了应对对有效治疗剂的关键需求，我们探索了全球健康优先箱，由疟疾药物风险公司(MMV)提供的240种化合物的集合。从这个游泳池里，flucofuron成为一个有希望的候选人，对两种家禽N.fowleri菌株的滋养体表现出很高的功效（ATCC30808IC50：2.58±0.64μM和ATCC30215IC50：2.47±0.38μM），甚至对抗性囊肿阶段有活性(IC50:0.88±0.07μM)。此外，氟呋喃诱导了多种代谢事件，表明触发了凋亡细胞死亡。这项研究强调了重新利用药物治疗挑战性疾病的潜力，比如PAM。
