Erath Jessey, Gallego-Delgado Julio, Xu Wenyue, Andriani Grasiella, Tanghe Scott, Gurova Katerina V, Gudkov Andrei, Purmal Andrei, Rydkina Elena, Rodriguez Ana
New York University School of Medicine, Department of Microbiology, Division of Parasitology, New York, New York, USA.
Roswell Park Cancer Institute, Department of Cell Stress Biology, Buffalo, New York, USA.
Antimicrob Agents Chemother. 2015 Mar;59(3):1427-34. doi: 10.1128/AAC.04704-14. Epub 2014 Dec 15.
Widespread resistance to most antimalaria drugs in use has prompted the search for novel candidate compounds with activity against Plasmodium asexual blood stages to be developed for treatment. In addition, the current malaria eradication programs require the development of drugs that are effective against all stages of the parasite life cycle. We have analyzed the antimalarial properties of xenomycins, a novel subclass of small molecule compounds initially isolated for anticancer activity and similarity to quinacrine in biological effects on mammalian cells. In vitro studies show potent activity of Xenomycins against Plasmodium falciparum. Oral administration of xenomycins in mouse models result in effective clearance of liver and blood asexual and sexual stages, as well as effective inhibition of transmission to mosquitoes. These characteristics position xenomycins as antimalarial candidates with potential activity in prevention, treatment and elimination of this disease.
目前使用的大多数抗疟疾药物存在广泛耐药性，这促使人们寻找对疟原虫无性血液阶段具有活性的新型候选化合物用于治疗。此外，当前的疟疾根除计划需要开发对寄生虫生命周期所有阶段均有效的药物。我们分析了异霉素的抗疟特性，异霉素是一类新型小分子化合物，最初因其抗癌活性以及在对哺乳动物细胞的生物学效应上与奎纳克林相似而被分离出来。体外研究表明异霉素对恶性疟原虫具有强大活性。在小鼠模型中口服异霉素可有效清除肝脏和血液中的无性和有性阶段疟原虫，还能有效抑制向蚊子的传播。这些特性使异霉素成为在预防、治疗和消除该疾病方面具有潜在活性的抗疟候选药物。
