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In Vitro Effect of DFC-2 on Mycolic Acid Biosynthesis in Mycobacterium tuberculosis

  • Kim, Sukyung (Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University) ;
  • Seo, Hoonhee (Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University) ;
  • Mahmud, Hafij Al (Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University) ;
  • Islam, Md Imtiazul (Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University) ;
  • Kim, Yong-Sik (Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University) ;
  • Lyu, Jiwon (Department of Pulmonary and Critical Care Medicine, School of Medicine, Soonchunhyang University) ;
  • Nam, Kung-Woo (Department of Life Science and Biotechnology, Soonchunhyang University) ;
  • Lee, Byung-Eui (Department of Life Science and Biotechnology Chemistry, Soonchunhyang University) ;
  • Lee, Kee-In (Green Chemistry Division, Korea Research Institute of Chemical Technology) ;
  • Song, Ho-Yeon (Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University)
  • 투고 : 2017.05.04
  • 심사 : 2017.09.04
  • 발행 : 2017.11.28

초록

DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to $0.39{\mu}g/ml$, DFC-2 inhibited both drugusceptible and -resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2's action in M. tuberculosis. The most affected functional gene category was "lipid biosynthesis," which is involved in mycolic acid synthesis. The decrease in transcription of genes related to mycolic acid synthesis was confirmed by RT-PCR. Furthermore, we found that DFC-2 triggered a reduction in mycolic acid levels, showing a similar pattern to that of mycolic acid synthesis inhibitor isoniazid. These results may explain how this compound kills mycobacteria efficiently by inhibiting mycolic acid synthesis.

키워드

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피인용 문헌

  1. Latest Comprehensive Knowledge of the Crosstalk between TLR Signaling and Mycobacteria and the Antigens Driving the Process vol.29, pp.10, 2019, https://doi.org/10.4014/jmb.1908.08057