Silver(I)-NHC Complexes as Dual-Action Agents Against Pathogenic Acanthamoeba Trophozoites: Anti-Amoebic and...

A series of six silver(I) complexes, namely bromo(1-benzyl-3-cinnamyl-benzimidazol-2-ylidene)silver (I) (1a), bromo[1-(4-methylbenzyl)-3-cinnamyl-benzimidazol-2-yliden]silver(I) (1b), bromo[1-(3-methoxylbenzyl)-3-cinnamyl-benzimidazol-2-yliden]silver(I) (1c), bromo[1-(3,5-dimethoxy-benzyl)-3-cinnamyl-benzimidazol-2-ylidene]silver(I) (1d), bromo[1-(naphthalen-1-ylmethyl)-3-cinnamyl-benzimidazol-2-ylidene]silver(I) (1e) and bromo[1-(pyren-1-ylmethyl)-3-cinnamyl-benzimidazol-2-yliden]silver(I) (1f), were synthetized and characterized by microanalyses and mass spectrometry and characterized by FT-IR and NMR spectroscopic techniques. The in vitro effects of silver(I) complexes on trophozoites of two Acanthamoeba isolates obtained from patients with keratitis were investigated. The parasites were exposed to concentrations of 10, 100 and 1000 µM for 24, 48 and 72 h. The complexes exhibited potent, dose- and time-dependent activity. Complete inhibition was observed within 24 h at a concentration of 1000 µM. At a concentration of 100 µM, complexes 1c-e exhibited reduced viability to less than 10% within 48 to 72 h. At a concentration of 10 µM, partial inhibition was observed. Preliminary morphological changes included the loss of acanthopodia, rounding, and detachment. These effects were not observed in the presence of the pre-ligands or commercially available silver compounds. Furthermore, molecular docking was utilized to analyze the molecules against Acanthamoeba castellanii CYP51, A. castellanii profilin IA, IB, and II. The highest recorded interactions were identified as -9.85 and -11.26 kcal/mol for 1e and 1f, respectively, when evaluated against the A. castellanii CYP51 structure.