DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae.
BACKGROUND:Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. Fo...
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ftdoajarticles:oai:doaj.org/article:9bd3f632227142ce9c2fd8c2dcf37ec8 2023-05-15T15:11:44+02:00 DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. Tomoyuki Yamaguchi Kazumasa Yokoyama Chie Nakajima Yasuhiko Suzuki 2016-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005013 https://doaj.org/article/9bd3f632227142ce9c2fd8c2dcf37ec8 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5040261?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005013 https://doaj.org/article/9bd3f632227142ce9c2fd8c2dcf37ec8 PLoS Neglected Tropical Diseases, Vol 10, Iss 9, p e0005013 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005013 2022-12-31T01:31:44Z BACKGROUND:Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. METHODOLOGY/PRINCIPAL FINDINGS:To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone-mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. CONCLUSIONS/SIGNIFICANCE:The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 9 e0005013 |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Tomoyuki Yamaguchi Kazumasa Yokoyama Chie Nakajima Yasuhiko Suzuki DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. METHODOLOGY/PRINCIPAL FINDINGS:To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone-mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. CONCLUSIONS/SIGNIFICANCE:The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans. |
format |
Article in Journal/Newspaper |
author |
Tomoyuki Yamaguchi Kazumasa Yokoyama Chie Nakajima Yasuhiko Suzuki |
author_facet |
Tomoyuki Yamaguchi Kazumasa Yokoyama Chie Nakajima Yasuhiko Suzuki |
author_sort |
Tomoyuki Yamaguchi |
title |
DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. |
title_short |
DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. |
title_full |
DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. |
title_fullStr |
DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. |
title_full_unstemmed |
DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae. |
title_sort |
dc-159a shows inhibitory activity against dna gyrases of mycobacterium leprae. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0005013 https://doaj.org/article/9bd3f632227142ce9c2fd8c2dcf37ec8 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 9, p e0005013 (2016) |
op_relation |
http://europepmc.org/articles/PMC5040261?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005013 https://doaj.org/article/9bd3f632227142ce9c2fd8c2dcf37ec8 |
op_doi |
https://doi.org/10.1371/journal.pntd.0005013 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
10 |
container_issue |
9 |
container_start_page |
e0005013 |
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1766342542563999744 |