Snapshot Profiling of the Antileishmanial Potency of Lead Compounds and Drug Candidates against Intracellular Leishmania donovani Amastigotes, with a Focus on Human-Derived Host Cells
Snapshot Profiling of the Antileishmanial Potency of Lead Compounds and Drug Candidates against Intracellular Leishmania donovani Amastigotes, with a Focus on Human-Derived Host Cells
复制标题
DOI：
10.1128/aac.01228-16
复制
发表时间：
2017-01
影响因子：
4.9
通讯作者：
Markela Koniordou;Stephen Patterson;S. Wyllie;K. Seifert
中科院分区：
文献类型：
--
作者：
Markela Koniordou;Stephen Patterson;S. Wyllie;K. Seifert
本研究描述了抗利什曼原虫药物对原代人巨噬细胞细胞内杜氏利什曼原虫无鞭毛体的体外效力，所述巨噬细胞在有或没有CD 14阳性单核细胞富集、佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）分化的THP-1细胞和小鼠腹膜渗出液巨噬细胞（PEM）的情况下获得。证实了五价和三价锑的宿主细胞依赖性效价。非昔硝唑对整个宿主细胞组的细胞内无鞭毛体无活性。非昔硝唑砜、（R）-PA-824、（S）-PA-824和VL-2098在所有检测的宿主细胞中显示出相似的效价。
ABSTRACT This study characterized the in vitro potencies of antileishmanial agents against intracellular Leishmania donovani amastigotes in primary human macrophages, obtained with or without CD14-positive monocyte enrichment, phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells, and mouse peritoneal exudate macrophages (PEMs). Host cell-dependent potency was confirmed for pentavalent and trivalent antimony. Fexinidazole was inactive against intracellular amastigotes across the host cell panel. Fexinidazole sulfone, (R)-PA-824, (S)-PA-824, and VL-2098 displayed similar potency in all of the host cells tested.