Screening of protease inhibitors as antiplasmodial agents. Part I: Aziridines and epoxides.
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.
Schulz
Franziska
F
Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Gelhaus
Christoph
C
Degel
Björn
B
Vicik
Radim
R
Heppner
Saskia
S
Breuning
Alexander
A
Leippe
Matthias
M
Gut
Jiri
J
Rosenthal
Philip J
PJ
Schirmeister
Tanja
T
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
D000962:Antimalarials; D001388:Aziridines; D004852:Epoxy Compounds; D011480:Protease Inhibitors