title: Inhibitors of Plasmepsin II-potential antimalarial agents.
abstract: 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.
authors.affiliation: Drug Discovery Chemistry and Biochemistry, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland. olivier.corminboeuf@actelion.com
authors.forename: Olivier
authors.initials: O
authors.lastname: Corminboeuf
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dunet
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hafsi
authors.forename: Julien
authors.initials: J
authors.lastname: Grimont
authors.forename: Corinna
authors.initials: C
authors.lastname: Grisostomi
authors.forename: Solange
authors.initials: S
authors.lastname: Meyer
authors.forename: Christoph
authors.initials: C
authors.lastname: Binkert
authors.forename: Daniel
authors.initials: D
authors.lastname: Bur
authors.forename: Andrew
authors.initials: A
authors.lastname: Jones
authors.forename: Lars
authors.initials: L
authors.lastname: Prade
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Christoph
authors.initials: C
authors.lastname: Boss
mesh_terms: 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
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II