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 hydrocloride (HCIP•HCl) (an antibiotic in clinical use) with the diphenyltin dichloride (Ph2SnCl2 DPTD). The complex was characterized in solid state by melting point, FT-IR, X-ray Powder Diffraction (XRPD) analysis, 119Sn Mossbauer spectroscopy, X-ray Fluorescence (XRF) spectroscopy, 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 were 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-folds), HCIP (up to 2.7-folds) or DPTD (>135-folds), towards the tested microbes. CIPTIN is classified to 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 microbe’s P. aeruginosa, E. coli, S. aureus and S. epidermidis to susceptible ones to CIPTIN. These IZ’s are greater to the corresponding ones of the HCIP•HCl by 1.1 to 1.5-folds against both Gram negative and positive bacteria tested. 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 μΜ). CIPTIN exhibits 2 to 9-folds lower MIC values against than its IC50 against HaCaT, while its genotoxic effect determined by micronucleus assay is equivalent to the corresponding ones of HCIP•HCl or HCIP.