A new calcium(II) complex of marbofloxacin showing much lower acute toxicity with retained antibacterial activity

摘要

Marbofloxacin (MB) is a newly developed veterinary drug with broad-spectrum antibacterial activity. In this study, a new calcium(II)-based complex of marbofloxacin, MB-Ca, was synthesized and structurally characterized by IR, ESI-MS, UV Vis and single crystal X-ray diffraction analysis. The characterization of this complex in solution state indicated that the coordinated MB-Ca was partly retained, along with the monomeric and dimeric forms of MB. It also showed satisfactory water solubility (1.89 mg/mL), comparing with MB (2.82 mg/mL) at 35 degrees C. The in vitro antibacterial activity of MB-Ca was also screened towards a series of typical pathogenic bacteria, and determined by the methods of turbidimetry and disc diffusion. The results indicated it showed comparable antibacterial activity to MB. However, it exhibited higher inhibitive ability in vitro on DNA gyrase than MB alone. Furthermore, MB-Ca showed significantly lower acute toxicity (LD50, 3186 mg/kg) than MB (LD50, 1294 mg/kg) in mice, based on the in vivo acute toxicity test. The histopathological examination on the major organs of the mice by the oral administration of MB-Ca did not show obvious organic lesions, which is similar to those treated by MB. The research results suggest that MB-Ca could be further developed into a new promising metal-based veterinary drug and a better substitute of MB, showing unabated antibacterial activity along with lower toxicity.