title: Synthesis, structures, and antimalarial activities of some silver(I), gold(I) and gold(III) complexes involving N-heterocyclic carbene ligands.
abstract: A series of mono-and dinuclear silver(I) and mononuclear gold(I) complexes containing bis(N-heterocyclic carbene) (NHC) or N-functionalized NHC ligands were synthesized and fully characterized by spectroscopic methods and, in some cases, by single crystal X-ray diffraction. The in vitro antiplasmodial and antifungal activities of a previously described family of N-functionalized bis(imidazolium) proligands and their corresponding silver(I), gold(I) and gold(III) complexes but also the new here described compounds were investigated in a chloroquine-resistant strain of Plasmodium falciparum, and against two Candida strains, respectively. For the first family, interesting antiplasmodial and antifungal activities were found for the dinuclear silver(I) species but they also showed strong hemolytic properties. Pharmaco-modulations leading to the second series of complexes allowed notably increase in the antiplasmodial activity, in particular of the mononuclear gold(I) complexes with IC(50) values up to 330 nM, without any hemolysis.
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, F-31077 Toulouse cedex 4, France. hemmert@lcc.toulouse.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Hemmert
authors.forename: Aymeric
authors.initials: A
authors.lastname: Fabié
authors.forename: Aude
authors.initials: A
authors.lastname: Fabre
authors.forename: Françoise
authors.initials: F
authors.lastname: Benoit-Vical
authors.forename: Heinz
authors.initials: H
authors.lastname: Gornitzka
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D012834:Silver / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D006571:Heterocyclic Compounds; D008024:Ligands; D009942:Organometallic Compounds; C030011:carbene; D012834:Silver; D006046:Gold; D008697:Methane