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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/35786
Title: Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones
Authors: Siriporn Kongsoi
Kazumasa Yokoyama
Apinun Suprasert
Fuangfa Utrarachkij
Chie Nakajima
Orasa Suthienkul
Yasuhiko Suzuki
Hokkaido University
Kissei Pharmaceutical Co., Ltd.
Kasetsart University
Mahidol University
Keywords: Chemistry;Environmental Science
Issue Date: 1-Jan-2015
Citation: Drug Testing and Analysis. Vol.7, No.8 (2015), 714-720
Abstract: © 2014 John Wiley & Sons, Ltd. Quinolones exhibit good antibacterial activity against Salmonella spp. isolates and are often the choice of treatment for life-threatening salmonellosis due to multi-drug resistant strains. To assess the properties of quinolones, we performed an in vitro assay to study the antibacterial activities of quinolones against recombinant DNA gyrase. We expressed the S. Typhimurium DNA gyrase A (GyrA) and B (GyrB) subunits in Escherichia coli. GyrA and GyrB were obtained at high purity (>95%) by nickel-nitrilotriacetic acid agarose resin column chromatography as His-tagged 97-kDa and 89-kDa proteins, respectively. Both subunits were shown to reconstitute an ATP-dependent DNA supercoiling activity. Drug concentrations that suppressed DNA supercoiling by 50% (IC<inf>50</inf>s) or generated DNA cleavage by 25% (CC<inf>25</inf>s) demonstrated that quinolones highly active against S. Typhimurium DNA gyrase share a fluorine atom at C-6. The relationships between the minimum inhibitory concentrations (MICs), IC<inf>50</inf>s and CC<inf>25</inf>s were assessed by estimating a linear regression between two components. MICs measured against S. Typhimurium NBRC 13245 correlated better with IC<inf>50</inf>s (R=0.9988) than CC<inf>25</inf>s (R=0.9685). These findings suggest that the DNA supercoiling inhibition assay may be a useful screening test to identify quinolones with promising activity against S. Typhimurium. The quinolone structure-activity relationship demonstrated here shows that C-8, the C-7 ring, the C-6 fluorine, and N-1 cyclopropyl substituents are desirable structural features in targeting S. Typhimurium gyrase.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84938798410&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/35786
ISSN: 19427611
19427603
Appears in Collections:Scopus 2011-2015

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