Navegando por Palavras-chave "Metallo-aminopeptidase inhibitors"

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    KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library
    (Pergamon-Elsevier Science Ltd, 2017) Gonzalez-Bacerio, Jorge; Maluf, Sarah El Chamy [UNIFESP]; Mendez, Yanira; Pascual, Isel; Florent, Isabelle; Melo, Pollyana Maria Saud [UNIFESP]; Budu, Alexandre [UNIFESP]; Ferreira, Juliana Conrado [UNIFESP]; Moreno, Ernesto; Carmona, Adriana Karaoglanovic [UNIFESP]; Rivera, Daniel G.; Rivero, Maday Alonso del; Gazarini, Marcos Leoni [UNIFESP]
    Malaria is a global human parasitic disease mainly caused by the protozoon Plasmodium falciparum. Increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. A novel target is the M1 alanyl-aminopeptidase from P. falciparum (PfA-M1), which is essential for parasite development in human erythrocytes and is inhibited by the pseudo-peptide bestatin. In this work, we used a combinatorial multicomponent approach to produce a library of peptidomimetics and screened it for the inhibition of recombinant PfA-M1 (rPfA-M1) and the in vitro growth of P. falciparum erythrocytic stages (3D7 and FcB1 strains). Dose-response studies with selected compounds allowed identifying the bestatin-based peptidomimetic KBE009 as a submicromolar rPfA-M1 inhibitor (K-i = 0.4 mu M) and an in vitro antimalarial compound as potent as bestatin (IC50 = 18 mu M