Synthesis, characterization, and antileishmanial activities of gold(I) complexes involving quinoline functionalized N-heterocyclic carbenes.
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.
Université de Toulouse, UPS, UMR 152 Pharma-DEV, Université Toulouse 3, Faculté des sciences pharmaceutiques, 35 Chemin des maraîchers, F-31062 Toulouse Cedex 9, France; Institut de Recherche pour le Développement, IRD, UMR 152 Pharma-DEV, F-31062 Toulouse Cedex 9, France.
Lucie
L
Paloque
CNRS, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, BP 44099, F-31077 Toulouse Cedex 4, France; Université de Toulouse, UPS, INPT, F-31077 Toulouse Cedex 4, France. Electronic address: hemmert@lcc.toulouse.fr.
Catherine
C
Hemmert
Université de Toulouse, UPS, UMR 152 Pharma-DEV, Université Toulouse 3, Faculté des sciences pharmaceutiques, 35 Chemin des maraîchers, F-31062 Toulouse Cedex 9, France; Institut de Recherche pour le Développement, IRD, UMR 152 Pharma-DEV, F-31062 Toulouse Cedex 9, France.
Alexis
A
Valentin
CNRS, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, BP 44099, F-31077 Toulouse Cedex 4, France; Université de Toulouse, UPS, INPT, F-31077 Toulouse Cedex 4, France.
Heinz
H
Gornitzka
D000818:Animals; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006046:Gold / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D018314:Leishmania infantum / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D006571:Heterocyclic Compounds; D050607:Organogold Compounds; D011804:Quinolines; D014344:Trypanocidal Agents; C030011:carbene; D006046:Gold; C037219:quinoline; D008697:Methane
Antileishmanial activity; Gold; J774A.1; Leishmania infantum; N-heterocyclic carbene; Quinoline