Journal of Infection and Chemotherapy

, Volume 2, Issue 3, pp 143–147 | Cite as

Structure-activity relationships between linkage style at the C-3 position and nuclear analogues of C(7)-hydroxyminoaminothiazol cephalosporins against methicillin-resistantStaphylococcus aureus

  • Hideaki Hanaki
  • Hiroshi Akagi
  • Toshio Otani
  • Keiichi Hiramatsu
Original Articles


We have previously shown that hydroxy-imino-aminothiazol at the 7-position was important to the antimethicillin-resistantStaphylococcus aureus (MRSA) activity of isocephems. In this study, in order to optimize the linkage style at the C-3 position and cephem backbones, 9 compounds were prepared by combining 3 cephem backbones with 3 different linkage styles at the C-3 position. The compounds had thiopyridinum-N-carbamoylmethyl fixed as the C-3 side chain and hydroxy-imino-aminothiazol at the C-7 position on the cephem backbones. The cephem backbones tested were cephem, isocephem, and 2-oxaisocephem. The linkage styles at the C-3 position were methylene, vinyl, and propylene linkages. Clinically isolated strains of MRSA were used to determine the MICs of the 9 compounds with different combinations of cephem backbones and linkage styles at the C-3 position. The compounds with vinyl linkage styles were more active against MRSA than the compounds with other linkage styles at the C-3 position, and among the cephem backbones with vinyl linkages, the cephem backbone exhibited the strongest anti-MRSA activity. MIC90s for cephem (1-S-V), isocephem (2-S-V), and 2-oxaisocephem (2-O-V) compounds were 1.56, 6.25, and 12.5 μg/mL, respectively, and the 1-S-V compound had the highest affinity to penicillin-binding protein 2′ among the 3 compounds with the vinyl-style linkage. Thus, the combination of cephem and a vinyl linkage at the C-3 position was shown to be optimal for anti-MRSA activity.

Key words

cephalosporin MRSA structure-activity relationship 


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Copyright information

© Japan Society of Chemotherapy 1996

Authors and Affiliations

  • Hideaki Hanaki
    • 1
  • Hiroshi Akagi
    • 2
  • Toshio Otani
    • 3
  • Keiichi Hiramatsu
    • 1
  1. 1.Department of BacteriologyJuntendo UniversityTokyoJapan
  2. 2.Ostuka Chemical Co LtdTokushimaJapan
  3. 3.Tokushima Research CenterTaiho Pharmaceutical Co LtdTokushimaJapan

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