Inhibitors of Plasmepsin II-potential antimalarial agents.
In order to overcome the problem of drug resistance in malaria, it appears wise to concentrate drug discovery efforts toward new structural classes and new mechanisms of action. We report our results, targeting Plasmepsin II, a Plasmodium falciparum aspartic protease active in hemoglobin degradation, a parasite specific catabolic pathway. The results show that the new structural class is not only inhibiting PMII in vitro but is also active in a P. falciparum infected human red blood cell assay.
Corminboeuf
Olivier
O
Drug Discovery Chemistry and Biochemistry, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland. olivier.corminboeuf@actelion.com
Dunet
Guillaume
G
Hafsi
Mehdi
M
Grimont
Julien
J
Grisostomi
Corinna
C
Meyer
Solange
S
Binkert
Christoph
C
Bur
Daniel
D
Jones
Andrew
A
Prade
Lars
L
Brun
Reto
R
Boss
Christoph
C
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D015800:Protozoan Proteins; D013329:Structure-Activity Relationship
D000962:Antimalarials; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II