Gallium(iii) and iron(iii) complexes of quinolone antimicrobials

Abstract

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.

Biofilm-specific uptake of a 4-pyridone-based iron chelator by Pseudomonas aeruginosa

“…This contrasted with DFP, which did not stimulate the antibiofilm activity of Ga 3? , so here only CP94 appears to show a ''Trojan Horse'' effect in which compounds may carry a toxic metal into cells (Golonka et al 2019;Mjos et al 2016). This effect has been demonstrated before in P. aeruginosa with a complex of Ga 3?…”

Gallium (Ga)–strontium (Sr) layered double hydroxide composite coating on titanium substrates for enhanced osteogenic and antibacterial abilities

“…Iron ions (Fe 3+ ) have been confirmed to be critical for almost all most microorganisms (fungi, gram-negative, and gram-positive bacteria) and play a vital role in oxidation-reduction electron transfer, DNA synthesis, enzyme mediation, oxidative stress defense systems, and other key processes. 48,49 However, several bacterial uptake systems cannot distinguish Ga 3+ from Fe 3+ , and Ga 3+ can induce an increase in ROS levels. 50,51 After calcination, the ROS levels of LDH250 in E. coli and S. aureus were significantly increased (Figure 7a).…”

Syntheses, structures, in vitro cytostatic activity and antifungal activity evaluation of four diorganotin(iv) complexes based on norfloxacin and levofloxacin

“…18,19 Furthermore, metal quinolone complexes, as an indivisible branch of quinolone derivatives, have been reported because of their high antibacterial effect and other potential biological activities. [20][21][22][23][24] For example, as reported by Debnath et al, the metal complex formed by norfloxacin, 2,2 0 -bipyridyl and chromium chloride [Cr(Nor)(Bipy)Cl 2 ]Cl showed high activity against four common phytopathogenic fungi, and the report pointed out that some metal complexes with appropriate ligands were more significant than the ligand itself in biological activities. 25 In addition, Kumar et al reported that the metal complexes formed by levofloxacin, bathophenanthroline and copper chloride [Cu(Lvx)(BPhen)Cl] showed strong inhibition against Streptococcus pneumoniae and E. coli at all concentrations.…”