title: Design, synthesis and antimalarial activity of novel, quinoline-based, zinc metallo-aminopeptidase inhibitors.
abstract: PfA-M1, a neutral zinc aminopeptidase of Plasmodium falciparum, is a new potential target for the discovery of antimalarials. The design and synthesis of a library of 45 quinoline-based inhibitors of PfA-M1 is reported. The best inhibitor displays an IC(50) of 854 nM. The antimalarial activity on a CQ-resistant strain and the specificity towards mammalian aminopeptidase N are also discussed.
authors.affiliation: UMR CNRS 8525, Institut Pasteur et Institut de Biologie de Lille, Université de Lille 2, Lille, France.
authors.forename: Marian
authors.initials: M
authors.lastname: Flipo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Florent
authors.forename: Philippe
authors.initials: P
authors.lastname: Grellier
authors.forename: Christian
authors.initials: C
authors.lastname: Sergheraert
authors.forename: Rebecca
authors.initials: R
authors.lastname: Deprez-Poulain
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry*
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D011804:Quinolines; D000626:Aminopeptidases; D015032:Zinc