Silver ciprofloxacin (CIPAG): a successful combination of chemically modified antibiotic in inorganic–organic hybrid

Abstract

The new silver(I) ionic, water soluble, compound {[Ag(CIPH)]NO∙0.75MeOH∙1.2HO} (CIPAG) was obtained by reacting silver(I) nitrate with the antibiotic ciprofloxacin (CIPH). The complex was characterized by m.p., mid-FT-IR, H-NMR, UV-Vis spectroscopic techniques. The crystal structures of both CIPAG and the hexahydrated neutral free drug {[CIPH]∙6(HO)} (2) were characterized by X-ray crystallography. Two neutral ligands are datively bonded to the metal ion through the piperidinic nitrogen atoms forming a cationic {[Ag(CIPH)]} counter part which is neutralized by a nitrate group. The antibacterial effect of CIPAG and the commercially available hydrochloric salt of the antibiotic ({[CIPH ]∙Cl } (3)) were tested against the bacterial species Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St. aureus) by the mean of minimum inhibitory concentration, minimum bactericidal concentration and their inhibitory zone (IZ). The influence of CIPAG and 3 against the formation of biofilm of PAO1 or St. aureus was also evaluated by mean of biofilm elimination concentration. The IZ caused by CIPAG which has been loaded in poly-hydroxyethylmethacrylate, is determined. The genotoxicity of CIPAG and 3 is tested in vitro against normal human corneal epithelial cells (HCET cells), by the presence of micronucleus in HCET cells and in vivo by mean of Allium cepa test.

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

“…The antibacterial studies show that PenAg is active against Gram negative (P. aeruginosa), contrary to penicillin itself, which is inactive. Silver(I) ions, on the other hand, show bacteriocidal activity against Gram negative (P. aeruginosa) [8,9]. Moreover, PenAg exhibits superior antibacterial activity to the free antibiotic against the Gram positive bacteria (S. epidermidis and S. aureus).…”

“…The effects of PenAg or PenNa on the growth of microbial strains: This study was performed according standard procedure, which is also described elsewhere [8][9][10][11][12]30]. Briefly, the bacterial strains were streaked onto in trypticase soy agar.…”

“…The growth was assessed after incubation for 20 h. The minimal inhibitory concentration (MIC) was determined as the concentration of the compound which inhibits the visible growth of the bacterium being investigated. The optical density of the solution at 620 nm compared to the concentrations graph led to the MIC determination [8][9][10][11][12]30].…”

“…Minimum bactericidal concentration testing: This study was performed according standard procedure which is also described elsewhere [8][9][10][11][12]31]. Bacteria were initially cultivated in the presence of PenAg in broth culture for 20 h. The MBC values were determined in duplicate, by subculturing 4 µL of the broth an agar plate [8][9][10][11][12]31]. Colony growth suggests non bactericidal activity of a metallodrug.…”

“…The conjugation of metals with drugs (CoMeDs) is a new research area for the discovery of new synergistic therapeutic modalities. CoMeDs combines two different agents, such as silver(I) with penicillin to create new agents with new properties from the superimposition of those initially possessed by the constituents [6][7][8][9][10][11][12]. Although the term "conjugate" is more properly used for polymer-drugs or dendrimer-drug conjugates where nanoparticles are formed, recently, the term CoMeD has also been used to emphasize the synergistic effect of the coordination of a metal with drugs [13,14].…”