Inhibitors of Plasmepsin II-potential antimalarial agents.
Corminboeuf O,
Dunet G,
Hafsi M,
Grimont J,
Grisostomi C,
Meyer S,
Binkert C,
Bur D,
Jones A,
Prade L,
Brun R,
Boss C.
Drug Discovery Chemistry and Biochemistry, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland. olivier.corminboeuf@actelion.com
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.
PMID: 17000102 [PubMed - indexed for MEDLINE]