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 characterized thein vitropotencies of antileishmanial agents against intracellularLeishmania donovaniamastigotes 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.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Markela
authors.initials: M
authors.lastname: Koniordou
authors.affiliation: School of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Patterson
authors.affiliation: School of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Wyllie
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom karin.seifert@lshtm.ac.uk.
authors.forename: Karin
authors.initials: K
authors.lastname: Seifert
mesh_terms: D000818:Animals; D000965:Antimony / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D054884:Host-Pathogen Interactions / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000469:parasitology; D009593:Nitroimidazoles / Q000494:pharmacology*; D061251:Primary Cell Culture; D013237:Stereoisomerism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D009593:Nitroimidazoles; C410767:pretomanid; C038307:fexinidazole; D000965:Antimony; D013755:Tetradecanoylphorbol Acetate
keywords: Leishmania donovani; drug potency; host cell