New insights in Au-NHCs complexes as anticancer agents

• Published in: European journal of medicinal chemistry Vol. 146; pp. 709 - 746
• Main Authors: Porchia, Marina, Pellei, Maura, Marinelli, Marika, Tisato, Francesco, Del Bello, Fabio, Santini, Carlo
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 25.02.2018
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor agents; Azolium salts; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Gold - chemistry; Gold - pharmacology; Gold(I); Gold(III); Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Medicinal chemistry; Methane - analogs & derivatives; Methane - chemistry; Methane - pharmacology; Molecular Structure; N-heterocyclic carbenes; Structure-Activity Relationship; Gold(III); Medicinal chemistry; Azolium salts; Antitumor agents; Gold(I); N-heterocyclic carbenes
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.01.065

Within the research field of antitumor metal-based agents alternative to platinum drugs, gold(I/III) coordination complexes have always been in the forefront due mainly to the familiarity of medicinal chemists with gold compounds, whose application in medicine goes back in the ancient times, and to the rich chemistry shown by this metal. In the last decade, N-heterocyclic carbene ligands (NHC), a class of ligands that largely resembles the chemical properties of phosphines, became of interest for gold(I) medicinal applications, and since then, the research on NHC-gold(I/III) coordination complexes as potential antiproliferative agents boosted dramatically. Different classes of gold(I/III)-NHC complexes often showed an outstanding in vitro antiproliferative activity, however up to now very few in vivo data have been reported to corroborate the in vitro results. This review summarizes all achievements in the field of gold (I/III) complexes comprising NHC ligands proposed as potential antiproliferative agents in the period 2004–2016, and critically analyses biological data (mainly IC50 values) in relation to the chemical structures of Au compounds. The state of art of the in vivo studies so far described is also reported. [Display omitted] •Potential antitumoral gold(I/III) complexes containing NHC ligands are reviewed.•The in vitro antiproliferative activities in terms of IC50 are cumulated.•A critical analysis of structure–activity relationships is elaborated.•The state of art of in vivo studies is reported.•The high potential of gold-NHC complexes as novel antitumoral drugs is highlighted.