title: In vitro activity of wALADin benzimidazoles against different life cycle stages of Plasmodium parasites.
abstract: wALADin1 benzimidazoles are specific inhibitors of δ-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 μM, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates.
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Lentz
authors.affiliation: University Hospital Heidelberg, Department for Infectious Diseases, Parasitology Unit, Heidelberg, Germany.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Sattler
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Fendler
authors.affiliation: University Hospital Heidelberg, Department for Infectious Diseases, Parasitology Unit, Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Gottwalt
authors.affiliation: LIMES Institute, Chemical Biology & Medicinal Chemistry Unit, Universität Bonn, Bonn, Germany.
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Halls
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Strassel
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Arriens
authors.affiliation: LIMES Institute, Chemical Biology & Medicinal Chemistry Unit, Universität Bonn, Bonn, Germany.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hannam
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: LIMES Institute, Chemical Biology & Medicinal Chemistry Unit, Universität Bonn, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Famulok
authors.affiliation: University Hospital Heidelberg, Department for Infectious Diseases, Parasitology Unit, Heidelberg, Germany.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Mueller
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Institute of Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany pfarr@microbiology-bonn.de.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Pfarr
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology; D014122:Toxoplasma / Q000187:drug effects
chemical_list: D000962:Antimalarials; D001562:Benzimidazoles; D013876:Thiophenes; C583087:wALADin1 compound; D000623:Porphobilinogen Synthase