Marbofloxacin combined with heavy rare-earth ions makes better candidates for veterinary drugs: crystal structure and bio-activity studies.

Marbofloxacin (MB) is a newly developed fluoroquinolone antibiotic used especially as a veterinary drug. It may be regarded as the improved version of enrofloxacin owing to its antibacterial activity, enhanced bioavailability, and pharmacokinetic–pharmacodynamic (PK–PD) properties. In this study, nine heavy rare-earth ions (Y, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu) were selected in light of their potential antibacterial activity and satisfactory biosafety to afford the corresponding rare-earth metal complexes of MB: the MB–Ln series. Their chemical structures and coordination patterns were characterized using IR spectroscopy, HRMS, TGA, and X-ray single-crystal diffraction analysis. Our results confirmed that all the MB–Ln complexes yielded the coincident coordination modes with four MB ligands coordinating to the Ln(III) center. In vitro antibacterial screening on five typical bacteria strains revealed that the MB–Ln complexes exhibited antibacterial activities comparable with MB, as indicated by the MIC/MBC values, in which Escherichia coli and Salmonella typhi were the most sensitive ones to MB–Ln. Furthermore, the MB–Ln complexes were found to be much less toxic in vivo than MB, as suggested by the evaluated LD₅₀ (50% lethal dose) values. All the MB–Ln series complexes fell in the LD₅₀ range of 5000–15 000 mg kg⁻¹, while the LD₅₀ value of MB was only 1294 mg kg⁻¹. Furthermore, MB–Lu, as the selected representative of MB–Ln, could effectively inhibit the activity of DNA gyrase, the same as MB, suggesting the primary antibacterial mechanism of the MB–Ln series. The results demonstrated the good prospects and potential of metal-based veterinary drugs with better drug performance. [ABSTRACT FROM AUTHOR]