open access

https://hdl.handle.net/2115/86975

Effectiveness of Fluoroquinolones with Difluoropyridine Derivatives as R1 Groups on the Salmonella DNA Gyrase in the Presence and Absence of Plasmid-Encoded Quinolone Resistance Protein QnrB19

英語

DNA gyrase

2021-10-14

Mary Ann Liebert

Microbial drug resistance

27(10)

1412-1419

Aims: WQ-3810 has strong inhibitory activity against Salmonella and other fluoroquinolone-resistant pathogens. The unique potentiality of this is attributed to 6-amino-3,5-difluoropyridine-2-yl at R1 group. The aim of this study was to examine WQ-3810 and its derivatives WQ-3334 and WQ-4065 as the new drug candidate for wild-type Salmonella and that carrying QnrB19. Materials and Methods: The half maximal inhibitory concentrations (IC(50)s) of WQ-3810, WQ-3334 (Br atom in place of methyl group at R8), and WQ-4065 (6-ethylamino-3,5-difluoropyridine-2-yl in place of 6-amino-3,5-difluoropyridine-2-yl group at R1) in the presence or absence of QnrB19 were assessed by in vitro DNA supercoiling assay utilizing recombinant DNA gyrase and QnrB19. Results: IC(50)s of WQ-3810, WQ-3334, and WQ-4065 against Salmonella DNA gyrase were 0.031 +/- 0.003, 0.068 +/- 0.016, and 0.72 +/- 0.39 mu g/mL, respectively, while QnrB19 increased IC(50)s of WQ-3810, WQ-3334, and WQ-4065 to 0.44 +/- 0.05, 0.92 +/- 0.34, and 9.16 +/- 2.21 mu g/mL, respectively. Conclusion: WQ-3810 and WQ-3334 showed stronger inhibitory activity against Salmonella Typhimurium DNA gyrases than WQ-4065 even in the presence of QnrB19. The results suggest that 6-amino-3,5-difluoropyridine-2-yl group at R1 is playing an important role and WQ-3810 and WQ-3334 to be good candidates for Salmonella carrying QnrB19.

学術雑誌論文

Accepted Manuscript

This is the accepted version of the following article: [Ruttana Pachanon, Kentaro Koide, Siriporn Kongsoi, Nami Ajima, Thoko Flav Kapalamula, Chie Nakajima, Orasa Suthienkul, and Yasuhiko Suzuki.Microbial Drug Resistance.ahead of printhttp://doi.org/10.1089/mdr.2020.0455], which has now been formally published in final form at Microbial Drug Resistance at [https://doi.org/10.1089/mdr.2020.0455]. This original submission version of the article may be used for non-commercial purposes in accordance with the Mary Ann Liebert, Inc., publishers’ self-archiving terms and conditions.

1076-6294