PUBLICATION
Structural characterization and pharmacological assessment in vitro/in vivo of a new copper(II)-based derivative of enrofloxacin
- Authors
- Guo, R.F., Yan, H.T., Liu, R.X., Li, H.C., Liu, Y.C., Chen, Z.F., Liang, H.
- ID
- ZDB-PUB-201212-19
- Date
- 2020
- Source
- Metallomics : integrated biometal science 12(12): 2145-2160 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/chemistry*
- Anti-Bacterial Agents/pharmacokinetics
- Anti-Bacterial Agents/pharmacology*
- Bacteria/drug effects
- Bacterial Infections/drug therapy
- Copper/chemistry*
- Copper/pharmacokinetics
- Copper/pharmacology*
- Enrofloxacin/analogs & derivatives*
- Enrofloxacin/pharmacokinetics
- Enrofloxacin/pharmacology*
- Escherichia coli/drug effects
- Humans
- Male
- Mice
- Rats, Sprague-Dawley
- Zebrafish
- PubMed
- 33300517 Full text @ Metallomics
Citation
Guo, R.F., Yan, H.T., Liu, R.X., Li, H.C., Liu, Y.C., Chen, Z.F., Liang, H. (2020) Structural characterization and pharmacological assessment in vitro/in vivo of a new copper(II)-based derivative of enrofloxacin. Metallomics : integrated biometal science. 12(12):2145-2160.
Abstract
Enrofloxacin (EFX) was selected as the medicinal ligand to afford a new copper(ii)-based complex, EFX-Cu, which was structurally characterized by spectroscopic analyses including X-ray single crystal diffraction. It was also stable and could retain the coordination state in aqueous solution. The in vitro antibacterial activity of EFX-Cu against a panel of pathogenic bacteria was about the same as that of EFX, except that it was twice as active against E. coli. The in vivo test on mice gave a LD50 value of 8148 mg kg-1 for EFX-Cu, which was much lower than those for EFX (LD50, 5312 mg kg-1) and its clinically used sodium salt, EFX-Na (LD50, 1421 mg kg-1). In addition, no obvious lesions in the organs of the dead mice were found by histopathological examination. Pharmacokinetic studies on rats suggested similar pharmacokinetics between EFX-Cu and EFX. On the other hand, EFX-Cu showed higher acute toxicity than EFX-Na in zebrafish, which was inconsistent with that in mice. The ROS-related inflammation and anti-inflammatory assay of EFX-Cu, respectively, in normal cells and zebrafish could be ascribed to its ROS-related redox property. Unfortunately, the final in vivo therapeutic assay in the E. coli-infected mouse model indicated that the therapeutic effect of EFX-Cu, mainly in terms of mortality in mice, was found to be lower than that of EFX-Na at the same dosage (800 mg kg-1, continuous gavage), although the contradictory factors between toxicity and antibacterial activity could not be excluded in this trial.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping