WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae

Jong Hoon Park, Tomoyuki Yamaguchi, Yuki Ouchi, Kentaro Koide, Shigetarou Mori, Hyun Kim, Tetsu Mukai, Chie Nakajima, Yasuhiko Suzuki

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background: Mycobacterium leprae causes leprosy and ofloxacin is used to control this bacterium. However, specific amino acid substitutions in DNA gyrases of M. leprae interferes with the effect of ofloxacin. Methodology/principal findings: Here we tested the inhibitory effect of WQ-3810 on DNA gyrases in M. leprae, using recombinant gyrases. We theorized that WQ-3810 and DNA gyrases interacted, which was tested in silico. Compared with control drugs like ofloxacin, WQ-3810 showed a better inhibitory effect on ofloxacin-resistant DNA gyrases. The in-silico study showed that, unlike control drugs, a specific linkage between a R1 group in WQ-3810 and aspartic acid at position 464 in the subunit B of DNA gyrases existed, which would enhance the inhibitory effect of WQ-3810. This linkage was confirmed in a further experiment, using recombinant DNA gyrases with amino acid substitutions in subunits B instead. Conclusions/significance: The inhibitory effect of WQ-3810 was likely enhanced by the specific linkage between a R1 group residue in its structure and DNA gyrases. Using interactions like the one found in the present work may help design new fluoroquinolones that contribute to halt the emergence of antibiotic-resistant pathogens.

Original languageEnglish
Pages (from-to)335-342
Number of pages8
JournalJournal of Infection and Chemotherapy
Issue number4
Publication statusPublished - Apr 2020
Externally publishedYes


  • DNA gyrase
  • Mycobacterium leprae
  • Recombinant molecules
  • WQ-3810

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases


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