Silver salts and
azole derivatives are well known for their antimicrobial properties. Recent evidence has demonstrated also their cytotoxic and genotoxic potential toward both normal and
cancer cells. Still, little is known about the action of complexes of
azoles with
silver(I)
salts. Thus, the goal of the study was to compare the chemical, cytotoxic and antimicrobial properties of
metronidazole complexes with
silver(I)
nitrate and
silver(I)
sulfate to
metronidazole and pure
silver(I)
salts. We synthetized a novel complex, [Ag(MTZ)2]2SO4, and confirmed its chemical structure and properties using 1H and 13C NMR spectroscopy and X-Ray, IR and elemental analysis. To establish the stability of complexes [Ag(MTZ)2NO3] and [Ag(MTZ)2]2SO4, they were exposed to daylight and UV-A rays and were visually assessed. Their cytotoxicity toward human
cancer cells (HepG2, Caco-2) and mice normal fibroblasts (Balb/c 3T3 clone A31) was determined by MTT, NRU, TPC and LDH assays. The micro-dilution broth method was used to evaluate their antimicrobial properties against Gram-positive and Gram-negative bacteria. A biofilm eradication study was also performed using the
crystal violet method and confocal
laser scanning microscopy. The photo-stability of the complexes was higher than
silver(I)
salts. In human
cancer cells, [Ag(MTZ)2]2SO4 was more cytotoxic than Ag2SO4 and, in turn, AgNO3 was more cytotoxic than [Ag(MTZ)2NO3]. For Balb/c 3T3 cells, Ag2SO4 was more cytotoxic than [Ag(MTZ)2]2SO4, while the cytotoxicity of AgNO3 and [Ag(MTZ)2NO3] was similar.
Metronidazole in the tested concentration range was non-cytotoxic for both normal and
cancer cells. The complexes showed increased bioactivity against aerobic and facultative anaerobic bacteria when compared to
metronidazole. For the majority of the tested bacterial strains, the
silver(I)
salts and complexes showed a higher antibacterial activity than MTZ; however, some bacterial strains presented the reverse effect. Our results showed that
silver(I) complexes present higher photo-stability, cytotoxicity and antimicrobial activity in comparison to MTZ and, to a certain extent, to
silver(I)
salts.