Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Current Topics: Communications to the Editor
Discovery of a Novel Fluoroquinolone Antibiotic Candidate WFQ-228 with Potent Antimicrobial Activity and the Potential to Overcome Major Drug Resistance
Tatsuya Hirano Tomohiko KinoshitaDaichi KazamoriSatoshi InoueKouji NishimuraAsuka SakuraiKensuke OhishiYasuhiro KuramotoHirotaka AmanoAkira Yazaki
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Supplementary material

2018 Volume 66 Issue 3 Pages 235-238

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Abstract

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.

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© 2018 The Pharmaceutical Society of Japan
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