title: Antiplasmodial activities of gold(I) complexes involving functionalized N-heterocyclic carbenes.
abstract: A series of twenty five molecules, including imidazolium salts functionalized by N-, O- or S-containing groups and their corresponding cationic, neutral or anionic gold(I) complexes were evaluated on Plasmodium falciparum in vitro and then on Vero cells to determine their selectivity. Among them, eight new compounds were synthesized and fully characterized by spectroscopic methods. The X-ray structures of three gold(I) complexes are presented. Except one complex (18), all the cationic gold(I) complexes show potent antiplasmodial activity with IC50 in the micro- and submicromolar range, correlated with their lipophilicity. Structure-activity relationships enable to evidence a lead-complex (21) displaying a good activity (IC50=210nM) close to the value obtained with chloroquine (IC50=514nM) and a weak cytotoxicity.
authors.affiliation: 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: Catherine.Hemmert@lcc-toulouse.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hemmert
authors.affiliation: 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; Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia.
authors.forename: Arba Pramundita
authors.initials: AP
authors.lastname: Ramadani
authors.affiliation: 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.
authors.forename: Luca
authors.initials: L
authors.lastname: Boselli
authors.affiliation: 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.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Fernández Álvarez
authors.affiliation: 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.
authors.forename: Lucie
authors.initials: L
authors.lastname: Paloque
authors.affiliation: 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.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Augereau
authors.affiliation: 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: Heinz.Gornitzka@lcc-toulouse.fr.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gornitzka
authors.affiliation: 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: Francoise.Vical@inserm.fr.
authors.forename: Françoise
authors.initials: F
authors.lastname: Benoit-Vical
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D010963:Plasmodium falciparum / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000962:Antimalarials; D009942:Organometallic Compounds; C030011:carbene; D006046:Gold; D002738:Chloroquine; D008697:Methane
keywords: Antiplasmodial drugs; Gold; N-Heterocyclic carbene; Organometallic complexes