In Vitro Evaluation of Silver-NHC Complexes Against a Clinical Isolate of Acanthamoeba castellanii: Time- and Dose-Dependent Effects

The synthesis of a series of six chloro[N-alkyl-N-cinnamyl-benzimidazol-2-yliden]silver(I) complexes was successfully achieved, wherein allyl (3a), methoxymethyl (3b), benzyl (3c), 3-fluorobenzyl (3d), 4-fluorobenzyl (3e) and 4-methyl-benzyl (3f) substituents were grafted on the benzimidazole ring. The isolated silver N-heterocyclic carbene (NHC) complexes were identified by microanalyses and mass spectrometry and characterized by FT-IR and NMR spectroscopic techniques. Conclusive evidence for the structures of complexes 3c and 3d was provided by single-crystal X-ray crystallography. The in vitro inhibitory activity of the six Ag-NHC complexes was tested against trophozoites and cysts of the pathogenic Acanthamoeba castellanii strain and the efficacy sequence is as follows: 3d > 3c > 3f > 3a > 3b > 3e. At a concentration of 100 µM in complexes 3c, 3d and 3f and after 72 h of incubation, 5.3, 3.2 and 6.3% A. castellanii trophozoite viabilities were observed, respectively. The utilization of elevated silver(I) drug concentrations, 1000 µM, resulted in the near-total eradication of pathogenic protozoa.