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  • 标题:Discovery of a Novel Fluoroquinolone Antibiotic Candidate WFQ-228 with Potent Antimicrobial Activity and the Potential to Overcome Major Drug Resistance
  • 本地全文:下载
  • 作者:Tatsuya Hirano ; Tomohiko Kinoshita ; Daichi Kazamori
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2018
  • 卷号:66
  • 期号:3
  • 页码:235-238
  • DOI:10.1248/cpb.c17-00717
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    WFQ-101 with a unique N -1 substituent, 5-amino-4-fluoro-2-(hydroxymethyl)phenyl group, was selected as a lead compound through combination screening based on antimicrobial activity and the efflux index against quinolone-resistant (QR) Pseudomonas aeruginosa ( P. aeruginosa ). Through structural optimization, we identified WFQ-228 as a novel fluoroquinolone antibiotic candidate. WFQ-228 had potent and superior activity in comparison to levofloxacin (LVX) and ciprofloxacin (CIP) against clinical isolates of P. aeruginosa , Escherichia coli and Acinetobacter baumannii , including QR strains. Furthermore, WFQ-228 demonstrated the potential to overcome major mechanisms of drug resistance; its antimicrobial activity was less affected by both pump-mediated efflux and mutations of the quinolone resistance-determining region in P. aeruginosa compared with LVX and CIP. These results suggest that WFQ-228 is a promising candidate for further evaluation in the treatment of infections caused by QR Gram-negative pathogens.

  • 关键词:novel fluoroquinolone;drug resistance;combination screening;structural optimization
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