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A Replicative In Vitro Assay for Drug Discovery against Leishmania donovani.一种用于发现抗杜氏利什曼原虫药物的体外复制分析方法。
Antimicrob Agents Chemother. 2016 May 23;60(6):3524-32. doi: 10.1128/AAC.01781-15. Print 2016 Jun.
2
Functional Validation of ABCA3 as a Miltefosine Transporter in Human Macrophages: IMPACT ON INTRACELLULAR SURVIVAL OF LEISHMANIA (VIANNIA) PANAMENSIS.ABCA3作为米替福新转运体在人巨噬细胞中的功能验证:对巴拿马利什曼原虫(维阿尼亚种)细胞内存活的影响
J Biol Chem. 2016 Apr 29;291(18):9638-47. doi: 10.1074/jbc.M115.688168. Epub 2016 Feb 22.
3
Leishmania survival in the macrophage: where the ends justify the means.利什曼原虫在巨噬细胞中的存活:只要目的正当,可以不择手段。
Curr Opin Microbiol. 2015 Aug;26:32-40. doi: 10.1016/j.mib.2015.04.007. Epub 2015 May 17.
4
Nitroimidazo-oxazole compound DNDI-VL-2098: an orally effective preclinical drug candidate for the treatment of visceral leishmaniasis.硝咪唑并恶唑类化合物 DNDI-VL-2098:一种治疗内脏利什曼病的有效口服前临床候选药物。
J Antimicrob Chemother. 2015 Feb;70(2):518-27. doi: 10.1093/jac/dku422. Epub 2014 Nov 10.
5
Leishmania panamensis infection and antimonial drugs modulate expression of macrophage drug transporters and metabolizing enzymes: impact on intracellular parasite survival.感染泛美利什曼原虫和锑制剂调节巨噬细胞药物转运体和代谢酶的表达:对细胞内寄生虫存活的影响。
J Antimicrob Chemother. 2014 Jan;69(1):139-49. doi: 10.1093/jac/dkt334. Epub 2013 Aug 24.
6
The R enantiomer of the antitubercular drug PA-824 as a potential oral treatment for visceral Leishmaniasis.抗结核药物 PA-824 的 R 对映异构体作为治疗内脏利什曼病的潜在口服药物。
Antimicrob Agents Chemother. 2013 Oct;57(10):4699-706. doi: 10.1128/AAC.00722-13. Epub 2013 Jul 15.
7
High content analysis of primary macrophages hosting proliferating Leishmania amastigotes: application to anti-leishmanial drug discovery.原代巨噬细胞中增殖利什曼原虫的高通量分析:在抗利什曼原虫药物发现中的应用。
PLoS Negl Trop Dis. 2013 Apr 4;7(4):e2154. doi: 10.1371/journal.pntd.0002154. Print 2013.
8
Comparison of a high-throughput high-content intracellular Leishmania donovani assay with an axenic amastigote assay.高通量高内涵细胞内利什曼原虫检测与无细胞内鞭毛体检测的比较。
Antimicrob Agents Chemother. 2013 Jul;57(7):2913-22. doi: 10.1128/AAC.02398-12. Epub 2013 Apr 9.
9
Oxygen tension modulates differentiation and primary macrophage functions in the human monocytic THP-1 cell line.氧张力调节人单核细胞 THP-1 细胞系的分化和原代巨噬细胞功能。
PLoS One. 2013;8(1):e54926. doi: 10.1371/journal.pone.0054926. Epub 2013 Jan 23.
10
Antimony-resistant but not antimony-sensitive Leishmania donovani up-regulates host IL-10 to overexpress multidrug-resistant protein 1.耐锑但不敏感的杜氏利什曼原虫上调宿主白细胞介素 10 以过表达多药耐药蛋白 1。
Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):E575-82. doi: 10.1073/pnas.1213839110. Epub 2013 Jan 22.

先导化合物和候选药物对细胞内杜氏利什曼原虫无鞭毛体的抗利什曼活性的快照分析,重点关注人源宿主细胞。

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.

作者信息

Koniordou Markela, Patterson Stephen, Wyllie Susan, Seifert Karin

机构信息

Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

School of Life Sciences, University of Dundee, Dundee, United Kingdom.

出版信息

Antimicrob Agents Chemother. 2017 Feb 23;61(3). doi: 10.1128/AAC.01228-16. Print 2017 Mar.

DOI:10.1128/AAC.01228-16
PMID:28069646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5328536/
Abstract

This study characterized the potencies of antileishmanial agents against intracellular 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, ()-PA-824, ()-PA-824, and VL-2098 displayed similar potency in all of the host cells tested.

摘要

本研究表征了抗利什曼原虫药物对原代人巨噬细胞内无鞭毛体的效力,这些原代人巨噬细胞通过有无CD14阳性单核细胞富集获得,佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)分化的THP-1细胞,以及小鼠腹腔渗出巨噬细胞(PEMs)。证实了五价和三价锑的宿主细胞依赖性效力。非昔硝唑对整个宿主细胞组中的细胞内无鞭毛体无活性。非昔硝唑砜、()-PA-824、()-PA-824和VL-2098在所有测试的宿主细胞中显示出相似的效力。