4.7 Article

Discovery of ferrocene-carborane derivatives as novel chemical antimicrobial agents against multidrug-resistant bacteria

Journal

SCIENCE CHINA-CHEMISTRY
Volume 55, Issue 11, Pages 2388-2395

Publisher

SCIENCE PRESS
DOI: 10.1007/s11426-012-4621-y

Keywords

multidrug-resistant bacteria; ferrocene-carborane derivatives; bactericidal effect; biocompatibility; minimal inhibitory concentration

Funding

  1. National Natural Science Foundation of China [21175020]
  2. National Key Basic Research Program [2010CB732404]
  3. Doctoral Fund of Ministry of Education of China [20090092110028]
  4. National High Technology Research and Development Program [2007AA022007]
  5. Guangdong Province [2011B090400357]
  6. Graduate Research and Innovation Program of Jiangsu Province [CXLX_0145]
  7. State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences

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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.

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