2. Academic Validation
  3. Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives

Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives

  • Bioorg Med Chem Lett. 2015 Jan 15;25(2):207-9. doi: 10.1016/j.bmcl.2014.11.073.
Elodie Jagu 1,  Rachid Djilali 1,  Sébastien Pomel 2,  Florence Ramiandrasoa 1,  Stéphanie Pethe 1,  Raphaël Labruère 3,  Philippe M Loiseau 4,  Casimir Blonski 5
Affiliations

Affiliations

  • 1 Chimie Bioorganique et Bioinorganique, LabEx LERMIT, CNRS, UMR 8182 (ICMMO), Bâtiment 420, Université Paris-Sud, 15 rue Georges Clemenceau, 91405 Orsay cedex, France.
  • 2 Chimiothérapie Antiparasitaire, LabEx LERMIT, Faculté de Pharmacie, CNRS, UMR 8076 (BioCIS), Université Paris-Sud, 5 rue Jean-Baptiste Clément, 92290 Châtenay-Malabry, France.
  • 3 Chimie Bioorganique et Bioinorganique, LabEx LERMIT, CNRS, UMR 8182 (ICMMO), Bâtiment 420, Université Paris-Sud, 15 rue Georges Clemenceau, 91405 Orsay cedex, France. Electronic address: raphael.labruere@u-psud.fr.
  • 4 Chimiothérapie Antiparasitaire, LabEx LERMIT, Faculté de Pharmacie, CNRS, UMR 8076 (BioCIS), Université Paris-Sud, 5 rue Jean-Baptiste Clément, 92290 Châtenay-Malabry, France. Electronic address: philippe.loiseau@u-psud.fr.
  • 5 Chimie Bioorganique et Bioinorganique, LabEx LERMIT, CNRS, UMR 8182 (ICMMO), Bâtiment 420, Université Paris-Sud, 15 rue Georges Clemenceau, 91405 Orsay cedex, France. Electronic address: casimir.blonski@u-psud.fr.
PMID: 25499437 DOI: 10.1016/j.bmcl.2014.11.073
Abstract

A structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. Among them, a spermidine derivative (compound 13) was specifically active in vitro against Leishmania donovani axenic amastigotes (IC50 at 5.4μM; Selectivity Index >18.5) and a spermine derivative (compound 28) specifically active against Trypanosoma brucei gambiense (IC50 at 1.9μM; Selectivity Index >52).

Keywords

Antikinetoplastids; Leishmania donovani; Polyamines; Trypanosoma brucei.

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