Design, synthesis and antimalarial activity of novel, quinoline-based, zinc metallo-aminopeptidase inhibitors

Marian Flipo; Isabelle Florent; Philippe Grellier; Christian Sergheraert; Rebecca Deprez-Poulain

doi:10.1016/s0960-894x(03)00550-x

Design, synthesis and antimalarial activity of novel, quinoline-based, zinc metallo-aminopeptidase inhibitors

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2659-62. doi: 10.1016/s0960-894x(03)00550-x.

Authors

Marian Flipo¹, Isabelle Florent, Philippe Grellier, Christian Sergheraert, Rebecca Deprez-Poulain

Affiliation

¹ UMR CNRS 8525, Institut Pasteur et Institut de Biologie de Lille, Université de Lille 2, Lille, France.

PMID: 12873488
DOI: 10.1016/s0960-894x(03)00550-x

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.

MeSH terms

Aminopeptidases / antagonists & inhibitors*
Aminopeptidases / genetics
Animals
Antimalarials / chemical synthesis*
Antimalarials / pharmacology
Drug Design
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Parasitic Sensitivity Tests
Plasmodium falciparum / drug effects
Quinolines / chemical synthesis*
Quinolines / pharmacology
Structure-Activity Relationship
Zinc / chemistry*

Substances

Antimalarials
Enzyme Inhibitors
Quinolines
Aminopeptidases
Zinc