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

Markella Koniordou, Stephen Patterson, Susan Wyllie, Karin Seifert (Lead / Corresponding author)

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Abstract

This study characterised in vitro potencies of anti-leishmanial 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 host cells tested.

Original languageEnglish
Article numbere01228
Pages (from-to)1-16
Number of pages16
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number3
Early online date9 Jan 2017
DOIs
Publication statusPublished - Mar 2017

Fingerprint

Leishmania donovani
Pharmaceutical Preparations
Antimony
Sulfones
Peritoneal Macrophages
Exudates and Transudates
Monocytes
Acetates
Macrophages
Lead
2-nitro-6-(4-(trifluoromethoxy)benzyloxy)-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazine
fexinidazole

Keywords

  • drug potency
  • host cell
  • Leishmania donovani

Cite this

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title = "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",
abstract = "This study characterised in vitro potencies of anti-leishmanial 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 host cells tested.",
keywords = "drug potency, host cell, Leishmania donovani",
author = "Markella Koniordou and Stephen Patterson and Susan Wyllie and Karin Seifert",
note = "This work was supported by the British Society for Antimicrobial Chemotherapy (grant reference GA2012_23R). K.S. was supported by a grant jointly funded by the UK Medical Research Council and the UK Department for International Development under the MRC/DFID Concordat agreement (grant reference MR/J008702/1). S. W. and S. P. are supported by a grant from the Wellcome Trust (079838). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.",
year = "2017",
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doi = "10.1128/AAC.01228-16",
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AU - Koniordou, Markella

AU - Patterson, Stephen

AU - Wyllie, Susan

AU - Seifert, Karin

N1 - This work was supported by the British Society for Antimicrobial Chemotherapy (grant reference GA2012_23R). K.S. was supported by a grant jointly funded by the UK Medical Research Council and the UK Department for International Development under the MRC/DFID Concordat agreement (grant reference MR/J008702/1). S. W. and S. P. are supported by a grant from the Wellcome Trust (079838). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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AB - This study characterised in vitro potencies of anti-leishmanial 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 host cells tested.

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