Gallium() and iron() complexes of quinolone antimicrobials

Iron is an essential nutrient for many microbes. According to the "Trojan Horse Hypothesis", biological systems have difficulties distinguishing between Fe 3+ and Ga 3+ , which constitutes the antimicrobial efficacy of the gallium( iii ) ion. Nine novel tris(quinolono)gallium( iii ) complexes and their corresponding iron( iii ) analogs have been synthesized and fully characterized. Quinolone antimicrobial agents from three drug generations were used in this study: ciprofloxacin, enoxacin, fleroxacin, levofloxacin, lomefloxacin, nalidixic acid, norfloxacin, oxolinic acid, and pipemidic acid. The antimicrobial efficacy of the tris(quinolono)gallium( iii ) complexes was studied against E. faecalis and S. aureus (both Gram-positive), as well as E. coli , K. pneumonia , and P. aeruginosa (all Gram-negative) in direct comparison to the tris(quinolono)iron( iii ) complexes and the corresponding free quinolone ligands at various concentrations. For the tris(quinolono)gallium( iii ) complexes, no combinational antimicrobial effects between Ga 3+ and the quinolone antimicrobial agents were observed. In an attempt to combine the antimicrobial properties of Ga 3+ and quinolone antimicrobial agents, tris(quinolono)gallium( iii ) complexes were prepared. In the style of the Ga 3+ vs. Fe 3+ "Trojan Horse" hypothesis, the bactericidal efficacy of these gallium( iii ) complexes was evaluated in direct comparison to their iron( iii ) analogs.