摘要
Antimicrobial resistance has now become a very serious global public health problem. New drug discovery and development are urgently needed to combat the growing threat of multidrug-resistant (MDR) bacteria. The aim of this study was to explore the potential application of three ferrocene-carborane derivatives as new promising agents to confront the problem of increasing antibiotic resistance. The results of agar diffusion bioassay, minimal inhibitory concentrations (MIC) testing and time-kill assay illustrate their broad-spectrum antimicrobial activities to both American Type Culture Collection (ATCC) control strains and MDR clinical isolates. It is evident that the relevant antimicrobial properties are all in a dose-dependent manner and gradually transform into a bactericidal effect from a bacteriostatic effect with the increasing of the drug concentration. Furthermore, these ferrocene-carborane derivatives have no/little toxic effect on normal cells like HELF cells and lead to little hemolysis at their MICs. This raises the possibility to develop novel antimicrobial drugs using these new ferrocene carborane derivants.
Antimicrobial resistance has now become a very serious global public health problem. New drug discovery and development are urgently needed to combat the growing threat of multidrug-resistant （MDR） bacteria. The aim of this study was to explore the potential application of three ferrocene-carborane derivatives as new promising agents to confront the problem of increas- ing antibiotic resistance. The results of agar diffusion bioassay, minimal inhibitory concentrations （MIC） testing and time-kill assay illustrate their broad-spectrum antimicrobial activities to both American Type Culture Collection （ATCC） control strains and MDR clinical isolates. It is evident that the relevant antimicrobial properties are all in a dose-dependent manner and grad- ually transform into a bactericidal effect from a bacteriostatic effect with the increasing of the drug concentration. Furthermore, these ferrocene-carborane derivatives have no/little toxic effect on normal cells like HELF cells and lead to little hemolysis at their MICs. This raises the possibility to develop novel antimicrobial drugs using these new ferrocene carborane derivants.
基金
supported by the National Natural Science Foundation of China (21175020)
National Key Basic Research Program (2010CB732404)
Doctoral Fund of Ministry of Education of China (20090092110028)
National High Technology Research and Development Program(2007AA022007)
Guangdong Province (2011B090400357)
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
关键词
多药耐药
二茂铁
衍生物
抗菌剂
硼烷
细菌
化学
公共卫生问题
multidrug-resistant bacteria, ferrocene-carborane derivatives, bactericidal effect, biocompatibility, minimal inhibitoryconcentration
