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
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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.