Anti-trypanosomal activity of cationic N-heterocyclic carbene gold(I) complexes

• Published in: Molecular and biochemical parasitology Vol. 214; pp. 112 - 120
• Main Authors: Winter, Isabel, Lockhauserbäumer, Julia, Lallinger-Kube, Gertrud, Schobert, Rainer, Ersfeld, Klaus, Biersack, Bernhard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2017
• Subjects: Anti-parasitic drugs; Antiprotozoal Agents - pharmacology; Cell Survival - drug effects; Coordination Complexes - pharmacology; Coordination Complexes - toxicity; Cytoskeleton; Epithelial Cells - drug effects; Flagella - drug effects; Gold; Gold - pharmacology; Gold - toxicity; HeLa Cells; Humans; Inhibitory Concentration 50; Methane - analogs & derivatives; Methane - pharmacology; Methane - toxicity; NHC complexes; Organometallics; Parasitic Sensitivity Tests; Trypanosoma brucei brucei - drug effects; Trypanosomes; Gold; BBB; Organometallics; AB assay; NHC; Trypanosomes; Cytoskeleton; HAT; NHC complexes; Anti-parasitic drugs; NTD
• ISSN: 0166-6851; 1872-9428
• DOI: 10.1016/j.molbiopara.2017.05.001

[Display omitted] •Gold(I) complexes 1a and 1b showed excellent in vitro activity against T. b. brucei.•1a and 1b quickly destroyed the cytoskeleton of T. b. brucei cells at low doses.•Reduced toxicity towards human HeLa cells was observed for 1a and 1b. Two gold(I) N-heterocyclic carbene complexes 1a and 1b were tested for their anti-trypanosomal activity against Trypanosoma brucei parasites. Both gold compounds exhibited excellent anti-trypanosomal activity (IC50=0.9–3.0nM). The effects of the gold complexes 1a and 1b on the T. b. brucei cytoskeleton were evaluated. Rapid detachment of the flagellum from the cell body occurred after treatment with the gold complexes. In addition, a quick and complete degeneration of the parasitic cytoskeleton was induced by the gold complexes, only the microtubules of the detached flagellum remained intact. Both gold compounds 1a and 1b feature selective anti-trypanosomal agents and were distinctly more active against T. b. brucei cells than against human HeLa cells. Thus, the gold complexes 1a and 1b feature promising drug candidates for the treatment of trypanosome infections such as sleeping sickness (human African Trypanosomiasis caused by Trypanosoma brucei parasites).