Synthesis, cytotoxicity and antibacterial studies of symmetrically and non‐symmetrically benzyl‐ or p‐cyanobenzyl‐substituted N‐Heterocyclic carbene–silver complexes

Abstract

From the reaction of 1H-imidazole (1a), 4,5-dichloro-1H-imidazole (1b) and 1H-benzimidazole (1c) with p-cyanobenzyl (8b) and (1-methyl-3-benzylbenzimidazole-2-ylidene) silver(I) acetate (8c) respectively. The four NHC-precursors 3a-c, 7c and four NHC-silver complexes 4a-c and 8c were characterized by single crystal X-ray diffraction. The preliminary antibacterial activity of all the compounds was studied against Gram-negative bacteria Escherichia coli, and Gram-positive bacteria Staphylococcus aureus using the qualitative Kirby-Bauer disc-diffusion method. All NHC-silver complexes exhibited medium to high antibacterial activity with areas of clearance ranging from 4 to 12 mm at the highest amount used, while the NHC-precursors showed significantly lower activity. In addition, all NHC-silver complexes underwent preliminary cytotoxicity tests on the human renal-cancer cell line Caki-1 and showed medium to high cytotoxicity with IC 50 values ranging from 53 (±8) to 3.2 (±0.6) µM.

Synthesis, Cytotoxicity and Antibacterial Studies of Novel Symmetrically and Nonsymmetrically 4‐(Methoxycarbonyl)benzyl‐Substituted N‐Heterocyclic Carbene–Silver Acetate Complexes

“…The previously synthesized NHC -AgOAc complexes in our laboratory showed an activity of up to 12 mm area of clearance at a concentration of 0.46 mmol for (1-benzyl-3-methylbenzimidazol-2-ylidene)silver(I) acetate [46]. Thus, the presented NHC -AgOAc complexes 4a -4f do not belong to the most promising drug candidates of the NHC -Ag series.…”

Ag(I)-N-heterocyclic carbene complexes of N-allyl substituted imidazol-2-ylidenes with ortho-, meta- and para-xylyl spacers: Synthesis, crystal structures and in vitro anticancer studies

“…The antiproliferative effects using MTT assay in HCT-116 cells after 72 h exposure to the imidazolium salts (7-10) and silver complexes (11)(12)(13)(14) were evaluated according to an established procedure [19]. For the experiments, the compounds (100 μL) were prepared freshly as stock solutions in DMSO and diluted with the HCT 116 cell culture medium to the final assay concentrations (0.1% V/V DMF).…”

“…Reactions involved in the syntheses of NHC precursors (7-10) and their respective Ag(I) bis-carbene complexes (11)(12)(13)(14) are summarized in Schemes 1 and 2, respectively. Bis-imidazoles with ortho-, metaand para-xylene cores [15] reacted with allyl bromide (2 equivalents) in acetonitrile to afford respective bis-imidazolium bromide salts as thick brown oils in good yield.…”

“…Salts 7-10 were non-hygroscopic, stable to air and moisture, and soluble in common organic solvents such as DMF, DMSO, acetone and acetonitrile. All imidazolium salts were fully characterized by 1 H, 13 C NMR, and elemental analysis. Additionally, we have reported the solid-state structure of salts 7, 8 and 9 were determined by single-crystal X-ray diffraction method [16][17][18].…”

“…Recently, Tacke and coworkers [13] reported a series of nitrilefunctionalized Ag(I)-NHC complexes derived from 4,5-dichloroimidazole and benzimidazole cores and their anticancer activity against Caki-1 cancer cell line. These functionalized Ag(I) mono-carbene complexes showed medium to high cytotoxicity with comparable IC 50 values.…”