Synthesis, characterization, and antileishmanial activities of gold(I) complexes involving quinoline functionalized N-heterocyclic carbenes

Eur J Med Chem. 2015 Apr 13:94:22-9. doi: 10.1016/j.ejmech.2015.02.046. Epub 2015 Feb 25.

Abstract

A series of new mononuclear cationic or neutral gold(I) complexes containing quinoline functionalized N-heterocyclic carbene(s) (NHC(s)) were synthesized and fully characterized by spectroscopic methods. The X-ray structures of two key compounds are presented. Proligands and their corresponding gold(I) complexes together with previously described silver(I) and gold(I) bis(NHC-quinoline) and gold(I) bis(NHC-methylbipyridine) complexes were evaluated in vitro towards Leishmania infantum. In parallel, the in vitro cytotoxicity of these molecules was assessed on the murine macrophages J774A.1. All gold(I) compounds show potent antileishmanial activity against L. infantum promastigotes and three of them are also efficient against L. infantum intracellular amastigotes. Structure-activity and toxicity relationships enables to evidence a lead-compound (6) displaying both a high activity and a good selectivity index.

Keywords: Antileishmanial activity; Gold; J774A.1; Leishmania infantum; N-heterocyclic carbene; Quinoline.

MeSH terms

  • Animals
  • Cell Line
  • Chemistry Techniques, Synthetic
  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical / methods
  • Gold / chemistry
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry
  • Leishmania infantum / drug effects*
  • Macrophages / drug effects
  • Methane / analogs & derivatives
  • Methane / chemistry
  • Mice
  • Molecular Structure
  • Organogold Compounds / chemical synthesis
  • Organogold Compounds / chemistry*
  • Organogold Compounds / pharmacology*
  • Quinolines / chemistry
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology*

Substances

  • Heterocyclic Compounds
  • Organogold Compounds
  • Quinolines
  • Trypanocidal Agents
  • carbene
  • Gold
  • quinoline
  • Methane