期刊
BIOMATERIALS
卷 34, 期 4, 页码 902-911出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.10.069
关键词
Antibacterial; Antibiofilm; Multidrug-resistant infection; Ferrocene-substituted carborane derivative; Staphylococcus aureus; Pseudomonas aeruginosa
资金
- National Key Basic Research Program [2010CB732404]
- National Nature Science Foundation of China [21175020, 20925104, 21021062]
- Key Project of Science and Technology of SuZhou [ZXY2012028]
- Doctoral Fund of Ministry of Education of China [20090092110028]
- National High Technology Research and Development Program [2007AA02 2007]
- Graduate Research and Innovation Program of Jiangsu Province [CXLX_0145]
- State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry Chinese Academy of Sciences
Multidrug resistance (MDR) of bacteria is still an unsolved serious problem to threaten the health of human beings. Developing new antibacterial agents, therefore, are urgently needed. Herein, we have explored the possibility to design and synthesize some novel antibacterial agents including ferrocene-substituted carborane derivative (Fc(2)SBCp(1)) and have evaluated the relevant antibacterial action against two clinical common MDR pathogens (i.e., Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa) in vitro and in vivo. The results demonstrate that in vitro antimicrobial activity of Fc(2)SBCp(1) could be gradually transformed into a bactericidal effect from a bacteriostatic effect with the increasing concentration of the active carborane derivative, which can also prevent biofilm formation at concentrations below MIC (i.e., minimal inhibitory concentration). Biocompatibility studies indicate that there exists no/or little toxic effect of Fc(2)SBCp(1) on normal cells/tissues and leads to little hemolysis. In vivo studies illustrate that the new carborane derivative Fc(2)SBCp(1) is highly effective in treating bacteremia caused by S. aureus and P. aeruginosa as well as interstitial pneumonia caused by S. aureus. This raises the possibility for the potential utilization of the new ferrocene-substituted carborane derivatives as promising antibacterial therapeutic agents against MDR bacterial infections in future clinical applications. (C) 2012 Elsevier Ltd. All rights reserved.
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