Antimicrobial activity of a ferrocene-substituted carborane derivative targeting multidrug-resistant infection

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• 作者：Shuihong Li^a ; Zhaojin Wang^b ; Yuanfeng Wei^c ; Changyu Wu^a ; Shengping Gao^a ; Hui Jiang^a ; Xinqing Zhao^d ; Hong Yan^b ; Xuemei Wang^a ; ^{xuewang@seu.edu.cn}
• 关键词：Antibacterial ; Antibiofilm ; Multidrug-resistant infection ; Ferrocene-substituted carborane derivative ; Staphylococcus aureus ; Pseudomonas aeruginosa
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：34
• 期：4
• 页码：902-911
• 全文大小：3003 K

文摘

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 (Fc₂SBCp₁) 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 Fc₂SBCp₁ 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 Fc₂SBCp₁ on normal cells/tissues and leads to little hemolysis. In?vivo studies illustrate that the new carborane derivative Fc₂SBCp₁ 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.