title: 4(1H)-Quinolones with liver stage activity against Plasmodium berghei.
abstract: With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luc(con)) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.
authors.affiliation: Department of Global Health, University of South Florida, Tampa, Florida, USA.
authors.forename: Alexis N
authors.initials: AN
authors.lastname: Lacrue
authors.forename: Fabián E
authors.initials: FE
authors.lastname: Sáenz
authors.forename: R Matthew
authors.initials: RM
authors.lastname: Cross
authors.forename: Kenneth O
authors.initials: KO
authors.lastname: Udenze
authors.forename: Andrii
authors.initials: A
authors.lastname: Monastyrskyi
authors.forename: Steven
authors.initials: S
authors.lastname: Stein
authors.forename: Tina S
authors.initials: TS
authors.lastname: Mutka
authors.forename: Roman
authors.initials: R
authors.lastname: Manetsch
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Kyle
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D005260:Female; D017930:Genes, Reporter; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000469:parasitology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000469:parasitology; D008156:Luciferases; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D030781:Organisms, Genetically Modified; D010962:Plasmodium berghei / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D034101:Sporozoites / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000962:Antimalarials; D015363:Quinolones; D008156:Luciferases