title: Preliminary LC-MS Based Screening for Inhibitors of Plasmodium falciparum Thioredoxin Reductase (PfTrxR) among a Set of Antimalarials from the Malaria Box.
abstract: Plasmodium falciparum thioredoxin reductase (PfTrxR) has been identified as a potential drug target to combat growing antimalarial drug resistance. Medicines for Malaria Venture (MMV) has pre-screened and identified a set of 400 antimalarial compounds called the Malaria Box. From those, we have evaluated their mechanisms of action through inhibition of PfTrxR and found new active chemical scaffolds. Five compounds with significant PfTrxR inhibitory activity, with IC50 values ranging from 0.9-7.5 µM against the target enzyme, were found out of the Malaria Box.
authors.affiliation: Department of Drug Discovery and Development, Auburn University, 4306 Walker Building, Auburn, AL 36849, USA. nkt0001@auburn.edu.
authors.forename: Neil K
authors.initials: NK
authors.lastname: Tiwari
authors.affiliation: Department of Drug Discovery and Development, Auburn University, 4306 Walker Building, Auburn, AL 36849, USA. jzy0028@tigermail.auburn.edu.
authors.forename: Priscilla J
authors.initials: PJ
authors.lastname: Reynolds
authors.affiliation: Department of Drug Discovery and Development, Auburn University, 4306 Walker Building, Auburn, AL 36849, USA. aic0001@auburn.edu.
authors.forename: Angela I
authors.initials: AI
authors.lastname: Calderón
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D002853:Chromatography, Liquid; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D013880:Thioredoxin-Disulfide Reductase
keywords: Malaria Box; Plasmodium falciparum thioredoxin reductase; antimalarial; screening for mechanism of action