title: Screening of protease inhibitors as antiplasmodial agents. Part I: Aziridines and epoxides.
abstract: A broad protease-based and cell-based screening of protease inhibitors yielded the aziridine-2-carboxylic acid derivative 2 a and the N-acylated aziridine-2,3-dicarboxylic acid derivatives 32 a and 34 b as the most potent inhibitors of falcipain-2 and falcipain-3 (IC(50) falcipain-2: 0.079-5.4 microM, falcipain-3: 0.25-39.8 microM). As the compounds also display in vitro activity against the P. falciparum parasite in the submicromolar and low micromolar range, these compound classes are leads for new antiplasmodial falcipain inhibitors.
authors.affiliation: Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schulz
authors.forename: Christoph
authors.initials: C
authors.lastname: Gelhaus
authors.forename: Björn
authors.initials: B
authors.lastname: Degel
authors.forename: Radim
authors.initials: R
authors.lastname: Vicik
authors.forename: Saskia
authors.initials: S
authors.lastname: Heppner
authors.forename: Alexander
authors.initials: A
authors.lastname: Breuning
authors.forename: Matthias
authors.initials: M
authors.lastname: Leippe
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D001388:Aziridines / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000962:Antimalarials; D001388:Aziridines; D004852:Epoxy Compounds; D011480:Protease Inhibitors