Antimalarial activity of azadipeptide nitriles.
Azadipeptide nitriles-novel cysteine protease inhibitors-display structure-dependent antimalarial activity against both chloroquine-sensitive and chloroquine-resistant lines of cultured Plasmodium falciparum malaria parasites. Inhibition of parasite's hemoglobin-degrading cysteine proteases was also investigated, revealing the azadipeptide nitriles as potent inhibitors of falcipain-2 and -3. A correlation between the cysteine protease-inhibiting activity and the antimalarial potential of the compounds was observed. These first generation azadipeptide nitriles represent a promising new class of compounds for antimalarial drug development.
Löser
Reik
R
Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. r.loeser@fzd.de
Gut
Jiri
J
Rosenthal
Philip J
PJ
Frizler
Maxim
M
Gütschow
Michael
M
Andrews
Katherine T
KT
D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001372:Aza Compounds / Q000737:chemistry*; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004151:Dipeptides / Q000737:chemistry*; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects
D000962:Antimalarials; D001372:Aza Compounds; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D009570:Nitriles; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C443101:falcipain 3