Silver(I) Complexes of the Pharmaceutical Agents Metronidazole and 4-Hydroxymethylpyridine: Comparison of Cytotoxic Profile for Potential Clinical Application

Abstract

In previous papers, we have reported on the high antifungal and significant antibacterial activity against Gram-positive and Gram-negative bacteria of the water-soluble silver(I) complexes of metronidazole and derivatives of pyridine compared to silver nitrate. In the present study, the cytotoxic activity of the silver(I) complexes of metronidazole and 4-hydroxymethylpyridine was compared with that of silver nitrate. Metronidazole and 4-hydroxymethylpyridine were investigated using Balb/c 3T3 and HepG2 cell lines in order to evaluate the potential clinical application of silver(I) complexes. The cells were exposed for 72 h to compounds at eight concentrations. The cytotoxic concentrations (IC50) of the study compounds were assessed within four biochemical endpoints: mitochondrial activity, lysosomal activity, cellular membrane integrity, and total protein content. The investigated silver(I) complexes displayed comparable cytotoxicity to that of silver nitrate used in clinics. Mean cytotoxic concentrations calculated for investigated silver(I) complexes from concentration–response curves ranged from 2.13 to 26.5 µM. HepG2 cells were less sensitive to the tested complexes compared to fibroblasts (Balb/c 3T3). However, the most affected endpoint for HepG2 cells was cellular membrane damage. The cytotoxicity of both silver complexes was comparable for Balb/c 3T3 cells. The cytotoxic potential of the new silver(I) compounds compared to that of silver nitrate used in medicine indicates that they are safe and could be used in clinical practice. The presented results are yet more stimulating to further studies that evaluate the therapeutic use of silver complexes.

Metalo components exhibiting significant anticancer and antibacterial properties: a novel sandwich-type like polymeric structure

“…These situations were consistent with the outcomes of TUNEL methods, and this finding was similar to those of previous studies [83][84][85][86][87] . According to information found in literature [88][89][90] , the appearance of the cells treated with 2, 3 and 4 clearly indicated the the quality and the number of cells in the flask monolayer were reduced.…”

Light Stability, Pro-Apoptotic and Genotoxic Properties of Silver (I) Complexes of Metronidazole and 4-Hydroxymethylpyridine against Pancreatic Cancer Cells In Vitro

“…The synthesis of the complex of the silver ion with metronidazole in the form of a nitrate salt was presented in our earlier papers [ 9 , 17 ]. The complex compound was synthesized in a simple one-step process by reacting AgNO 3 with metronidazole (1:2) ( Scheme 1 ) in water [ 9 ]. We confirmed the good reaction yield and purity of the resulting product (see Materials and Methods section).…”

“…In some cases, silver nitrate as such or in the form of concentrated solutions is used for cauterization, warts, and the like. It was also demonstrated that silver ions (silver nitrate) exerted cytotoxic and genotoxic properties against different human cells via oxidative stress production [ 8 , 9 ]. Recently, anticancer action of silver nitrates related to apoptosis induction was demonstrated in H-ras 5RP7 cells [ 10 ].…”

“…Complex compounds of silver and metronidazole (MTZ) and 4-hydroxymethylpyridine (4-OHMePy) have been presented in our earlier papers [ 9 , 16 , 17 ]. In our current research, we aimed to evaluate whether cytotoxicity of silver nitrate and its complexes may be a result of apoptosis.…”

Prosopis juliflora leave extracts induce cell death of MCF-7, HepG2, and LS-174T cancer cell lines

“…All of those major compounds involved in P. juliflora were approved as anticancer agents in several studies. The cytostatic or cytotoxic properties of the hydroxy-methylpyridine were recently investigated by several studies (Radko et al, 2019[ 27 ]). Nicotinamide (NAM), the amide form of niacin (i.e.…”