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

doi:10.1128/AAC.01228-16

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)

Biological Chemistry and Drug Discovery

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

174 Downloads (Pure)

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 language	English
Article number	e01228
Pages (from-to)	1-16
Number of pages	16
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	3
Early online date	9 Jan 2017
DOIs	https://doi.org/10.1128/AAC.01228-16
Publication status	Published - Mar 2017

Keywords

drug potency
host cell
Leishmania donovani

Access to Document

10.1128/AAC.01228-16

Author Accepted ManuscriptAccepted author manuscript, 162 KB

Aref#d: 18185. Characterization and validation of drug targets in the Kinetoplastida (Principal Research Fellowship/Programme Grant)
Fairlamb, A. (Investigator)
1/10/06 → 30/09/17
Project: Research

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",

language = "English",

volume = "61",

pages = "1--16",

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publisher = "American Society for Microbiology",

number = "3",

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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. / Koniordou, Markella; Patterson, Stephen ; Wyllie, Susan et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 3, e01228, 03.2017, p. 1-16.

Research output: Contribution to journal › Article › peer-review

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AU - Wyllie, Susan

AU - Seifert, Karin

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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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KW - host cell

KW - Leishmania donovani

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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

Keywords

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Aref#d: 18185. Characterization and validation of drug targets in the Kinetoplastida (Principal Research Fellowship/Programme Grant)

Cite this