Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Comparative Superiority of in vitro Activity of DW-224a Supported by the Downward MIC Distribution in Ciprofloxacin-resistant Staphylococcus aureus

시프로플록사신 내성 황색 포도상 구균에서 MIC의 하향 분포로 입증된 DW-224a의 in vitro 항균 활성의 비교 우수성

  • Yoon, Eun-Jeong (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Lee, Chun-Yeong (Department of Life Science, University of Seou) ;
  • Lee, Jong-Seo (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Choe, Eung-Chil (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Shim, Mi-Ja (Department of Life Science, University of Seoul)
  • 윤은정 (서울대학교 약학대학종합 약학 연구소) ;
  • 이춘영 (서울시립대학교 생명과학과) ;
  • 이종서 (서울대학교 약학대학종합 약학 연구소) ;
  • 최응칠 (서울대학교 약학대학종합 약학 연구소) ;
  • 심미자 (서울시립대학교 생명과학과)
  • Published : 2009.12.20
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Abstract

The comparative superior in vitro activity of DW-224a was supported by the downward MIC distribution due to the weakened influence of alterations within target enzymes in ciprofloxacin-resistant Staphylococcus aureus. The MI$C_{50}$ for DW-224a was 4 $\mu$g/mL, similar to that of gemifloxacin, 8-fold less than that of sparfloxacin and 16-over-fold less than that of ciprofloxacin. We constructed combinations of amino acid changes, located at codon 80, 83 or 84 within GrlA and 84, 85 or 88 within GyrA, which were associated with MIC increase. The amino acid changes were less influential to the MIC of DW-224a compared to those of other fluoroquinolones, and it was verified from the requirement of a total of two GrlA- and two GyrA-alterations to reach the MIC of DW-224a over 32 $\mu$g/mL.

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References

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