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

Marian Flipo , Isabelle Florent , Philippe Grellier (1) , Christian Sergheraert (2) , Rebecca Déprez-Poulain (3)

1 MCAM - Molécules de Communication et Adaptation des Micro-organismes
2 Université de Lille, Droit et Santé
3 Biostructures et Decouverte de Medicament

PfA-M1, a neutral zinc aminopeptidase of Plasmodium falciparum, is a new potential target for the discovery of anti-malarials. 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. #

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology; Life Sciences [q-bio]; Microbiology and Parasitology; Chemical Sciences

Marian Flipo, Isabelle Florent, Philippe Grellier, Christian Sergheraert, Rebecca Déprez-Poulain. Design, synthesis and antimalarial activity of novel, quinoline-Based, zinc metallo-aminopeptidase inhibitors. Bioorganic and Medicinal Chemistry Letters, 2003, 13 (16), pp.2659-2662. ⟨10.1016/S0960-894X(03)00550-X⟩. ⟨mnhn-02867485⟩