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

Lucie Paloque (1) , Catherine Hemmert (2) , Alexis Valentin (1) , Heinz Gornitzka (2)

1 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
2 LCC - Laboratoire de chimie de coordination

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.

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

Domaines: Chimie thérapeutique; Chimie de coordination

Lucie Paloque, Catherine Hemmert, Alexis Valentin, Heinz Gornitzka. Synthesis, characterization, and antileishmanial activities of gold(I) complexes involving quinoline functionalized N-heterocyclic carbenes. European Journal of Medicinal Chemistry, 2015, 94, pp.22-29. ⟨10.1016/j.ejmech.2015.02.046⟩. ⟨hal-01925132⟩