A New Calcium(II)-Based Substitute for Enrofloxacin with Improved Medicinal Potential
Hou-Tian Yan,
Rui-Xue Liu,
Qi-Zhen Yang,
Yan-Cheng Liu,
Hong-Chang Li,
Rui-Feng Guo,
Lin-Hua Wu,
Li-Min Liu,
Hong Liang
Affiliations
Hou-Tian Yan
School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China
Rui-Xue Liu
School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China
Qi-Zhen Yang
School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China
Yan-Cheng Liu
School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China
Hong-Chang Li
School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China
Rui-Feng Guo
School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China
Lin-Hua Wu
College of Pharmacy, Guangxi Medical University, Nanning 530021, China
Li-Min Liu
College of Pharmacy, Guangxi Medical University, Nanning 530021, China
Hong Liang
School of Chemistry & Pharmaceutical Sciences, State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China
Enrofloxacin (EFX) reacting with Ca(II) afforded a new complex, [Ca(EFX)2(H2O)4] (EFX-Ca), which was structurally characterized both in solid and solution chemistry. E. coli and S. typhi were tested to be the most sensitive strains for EFX-Ca. The LD50 value of EFX-Ca in mice was 7736 mg/kg, implying the coordination of EFX to Ca(II) effectively reduced its acute toxicity. EFX-Ca also decreased the plasma-binding rate and enhanced the drug distribution in rats along with longer elimination half-life. EFX-Ca also showed similar low in vivo acute toxicity and higher anti-inflammation induced by H2O2 or CuSO4 in zebrafish, with reactive oxygen species (ROS)-related elimination. The therapeutic effects of EFX-Ca on two types (AA and 817) of E. coli-infected broilers were also better than those of EFX, with cure rates of 78% and 88%, respectively. EFX-Ca showed promise as a bio-safe metal-based veterinary drug with good efficacy and lower toxicity.
