Ciprofloxacin conjugated to diphenyltin(IV): a novel formulation with enhanced antimicrobial activity.

The metalloantibiotic of formula Ph2Sn(CIP)2 (CIPTIN) (HCIP = ciprofloxacin) was synthesized by reacting ciprofloxacin hydrochloride (HCIP·HCl) (an antibiotic in clinical use) with diphenyltin dichloride (Ph2SnCl2DPTD). The complex was characterized in the solid state by melting point, FT-IR, X-ray Powder Diffraction (XRPD) analysis, 119Sn Mössbauer spectroscopy, X-ray Fluorescence (XRF) spectroscopy, and Thermogravimetry/Differential Thermal Analysis (TG-DTA) and in solution by UV-Vis, 1H NMR spectroscopic techniques and Electrospray Ionisation Mass Spectrometry (ESI-MS). The crystal structure of CIPTIN and its processor HCIP was also determined by X-ray crystallography. The antibacterial activity of CIPTIN, HCIP·HCl, HCIP and DPTD was evaluated against the bacterial species Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), by the means of Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Inhibition Zones (IZs). CIPTIN shows lower MIC values than those of HCIP·HCl (up to 4.2-fold), HCIP (up to 2.7-fold) or DPTD (>135-fold), towards the tested microbes. CIPTIN is classified into bactericidal agents according to MBC/MIC values. The developing IZs are 40.8 ± 1.5, 34.0 ± 0.8, 36.0 ± 1.1 and 42.7 ± 0.8 mm, respectively which classify the microbes P. aeruginosa, E. coli, S. aureus and S. epidermidis to susceptible ones to CIPTIN. These IZs are greater than the corresponding ones of HCIP·HCl by 1.1 to 1.5-fold against both the tested Gram negative and Gram positive bacteria. CIPTIN eradicates the biofilm of P. aeruginosa and S. aureus more efficiently than HCIP·HCl and HCIP. The in vitro toxicity and genotoxicity of CIPTIN were tested against human skin keratinocyte cells (HaCaT) (IC50 = 2.33 µM). CIPTIN exhibits 2 to 9-fold lower MIC values than its IC50 against HaCaT, while its genotoxic effect determined by micronucleus assay is equivalent to the corresponding ones of HCIP·HCl or HCIP.

A water-soluble silver(I) formulation as an effective disinfectant of contact lenses cases.

The antibacterial effect of the already known water-soluble compound {[Ag6(µ3-Hmna)4(µ3-mna)2]2-·[(Et3NH)+]2·(DMSO)2·(H2O)} (AGMNA) (H2mna = 2­mercapto­nicotinic acid) was evaluated by the mean of the Minimum Inhibitory Concentration (MIC), the Minimum Bactericidal Concentration (MBC) and the Inhibitory Zone (IZ), against the bacterial strains Pseudomonas aeruginosa (PAO1) and Staphylococcus aureus (St. aureus) which settle in the cornea, in bacterial keratitis. The MICs' of AGMNA against PAO1 and St. aureus were 25.7 ±â€¯2.4 µM and 42.0 ±â€¯0.3 µM respectively. Τhe Biofilm Elimination Concentration (ΒΕC) was used to evaluate the influence of AGMNA on the formation of biofilm of PAO1. AGMNA exhibits stronger antimicrobial activity than that of H2mna or AgNO3. The toxicity of AGMNA was examined against normal human corneal epithelial cells (HCET cells) and by micronucleus (MN) assay in HCET cells. Thus, the IC50 value of AGMNA, towards HCET cells is higher than 120 µΜ, while its effect on MN frequency, of HCET cells, is meaningless, when they are treated with it at 120 µΜ, suggesting no in vitro genotoxicity. The Mitotic Index (MI), Chromosomal Aberrations (CA) and Nuclear Abnormalities (NA) analyses of Allium cepa reveal insignificant variations between treated and untreated ones indicating no in vivo genotoxicity.

Chloro(triphenylphosphine)gold(I) a forefront reagent in gold chemistry as apoptotic agent for cancer cells.

The antiproliferative activity of the gold complex [Au(tpp)Cl] (1) (tpp=triphenyphosphine) against human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblast cells (MRC-5) was investigated. The compound exhibits stronger activity against MCF-7 cells than cisplatin. The apoptotic pathway, especially though the mitochondrion damage was concluded by cell cycle arrest, flow cytometry using Annexin V-Fluorescein IsoThioCyanate (FITC) and Propidium Iodide (PI) as indicators, assays and permeabilization of the mitochondrial membrane tests. The molecular mechanism of action of 1 was further studied by: (i) its catalytic activity on the oxidation of linoleic acid (an acid that partakes in membrane fluidity) to hyperoxolinoleic acid by oxygen and (ii) its binding affinity towards the calf thymus (CT) DNA. Since the deactivation of cisplatin by glutathione (GSH), is related with the development of cell resistance, the reaction of 1 with GSH was investigated by UV absorption spectroscopy. The absence of micronucleus in cells confirms that the complex has no in vitro toxicity. The in vivo genotoxicity caused by 1 was evaluated by Allium cepa test.