Introduction: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use. Methods: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated. Results: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01±4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD 50 ) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride. Conclusion: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.
Three new 4-phenylcoumarins, mesuaferlinns A-C (1-3), together with ten known 4-phenylcoumarins, 4-13, were isolated from the branches and leaves of Mesua ferrea Linn. (Clusiaceae). The structure of compounds 1-3 were determined on the basis of spectroscopic methods including extensive analysis of NMR and mass spectroscopic data. Ten 4-phenylcoumarins were tested for their cytochrome P450 family 1 enzymes (CYP 1A1, CYP 1A2, and CYP 1B1) inhibitory effects. Compounds 5 and 10 were found to be the most potent two CYP1B1 inhibitors with inhibitory viabilities values of 56.64% and 47.46%.
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