title: Inhibitors of the Plasmodium falciparum parasite aspartic protease plasmepsin II as potential antimalarial agents.
abstract: Malaria is a very serious infectious disease against which the currently available drugs are loosing effectiveness. The main problem is the emergence and the spreading of resistant parasite strains. New treatments are needed in order to regain control over the disease. Drug discovery efforts towards this goal are likely to be more successful, if they focus towards novel mechanisms of action. Such efforts will result in drugs that are functionally and structurally different from the existing drugs and therefore will overcome existing resistances. Here we focus on the aspartic protease plasmepsin II, which is a promising new drug target. We review the drug discovery efforts that were published in the literature on this enzyme, and we present the compounds synthesized at Actelion Pharmaceuticals Ltd.
authors.affiliation: Drug Discovery Chemistry, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil / BL, Switzerland. christoph.boss@actelion.com
authors.forename: C
authors.initials: C
authors.lastname: Boss
authors.forename: S
authors.initials: S
authors.lastname: Richard-Bildstein
authors.forename: T
authors.initials: T
authors.lastname: Weller
authors.forename: W
authors.initials: W
authors.lastname: Fischli
authors.forename: S
authors.initials: S
authors.lastname: Meyer
authors.forename: C
authors.initials: C
authors.lastname: Binkert
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D020650:Combinatorial Chemistry Techniques; D005021:Ethylamines / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D018716:Molecular Mimicry; D010654:Phenylbutyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D015800:Protozoan Proteins; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D005021:Ethylamines; D010654:Phenylbutyrates; D010880:Piperidines; D011480:Protease Inhibitors; D015800:Protozoan Proteins; C034940:3-amino-2-hydroxy-4-phenylbutanoic acid; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II