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

• Published in: Journal of inorganic biochemistry 2020-02, Vol.203, p.110905, Article 110905
• Main Authors: Xie, Yan-Jie, Yu, Meng-Xin, Yang, Qi-Zhen, Liu, Yan-Cheng, Liu, Rui-Xue, Dong, Jia-Xin, Wu, Xiao-Ye, Guo, Rui-Feng, Pan, Yu-Xing, Chen, Zhen-Feng, Liang, Hong
• Format: Article
• Language: English
• Subjects: Acute toxicity; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - toxicity; Antibacterial activity; Bacteria - drug effects; Calcium - chemistry; Calcium complex; Coordination Complexes - chemical synthesis; Coordination Complexes - toxicity; DNA gyrase; Fluoroquinolones - chemistry; Hepatocytes - drug effects; Marbofloxacin; Mice; Organometallic Compounds - chemical synthesis; Organometallic Compounds - toxicity; Veterinary drug
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2019.110905

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 °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. The first calcium(II) complex of marbofloxacin (MB) was reported in it crystal structure and solution chemistry, which showed similar antibacterial activity to MB, but much lower acute toxicity, suggesting a better substitute for MB. [Display omitted] •The first Ca(II) complex of marbofloxacin (MB) was reported with its crystal structure.•The complex, MB-Ca, showed similar antibacterial activity to MB.•MB-Ca did not show obvious organic lesions on the major organs of the tested mice.•MB-Ca showed much lower acute toxicity than MB, suggesting a better substitute for MB.