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Int J Antimicrob Agents. 2019 Jul;54(1):69-74. doi: 10.1016/j.ijantimicag.2019.02.013. Epub 2019 Feb 23.

In vitro activity of DNF-3 against drug-resistant Mycobacterium tuberculosis.

Author information

1
Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31151, South Korea.
2
Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31151, South Korea; Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Gumi, Gyeongbuk 39371, South Korea.
3
Regional Innovation Center, Soonchunhyang University, Asan, Chungnam 31538, South Korea.
4
Department of Life Science and Biotechnology, Soonchunhyang University, Asan, Chungnam 31538, South Korea.
5
Green Chemistry Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea.
6
Green Chemistry Division, Korea Research Institute of Chemical Technology, Daejeon 34114, South Korea; Major of Green Chemistry and Environmental Biotechnology, University of Science & Technology, Daejeon 34113, South Korea.
7
Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam 31151, South Korea; Regional Innovation Center, Soonchunhyang University, Asan, Chungnam 31538, South Korea. Electronic address: songmic@sch.ac.kr.

Abstract

Due to the emergence of multidrug-resistant and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, new antituberculosis drugs are urgently required to improve the efficacy of current tuberculosis (TB) treatment. To achieve this goal, ca. 1000 chemical compounds were screened for potential antimycobacterial activity, among which methyl 5-(2-diethylaminoethoxy)-7,12-dioxo-7,12 dihydrodinaphtho[1,2-b;2',3'-d]furan-6-carboxylate (DNF-3) showed strong activity against all of the tested drug-susceptible and -resistant M. tuberculosis strains, with 50% minimum inhibitory concentrations (MIC50 values) of 0.02-0.39 µg/mL both in culture broth and within murine RAW 264.7 macrophage cells. When DNF-3 was used in combination with rifampicin or streptomycin, it exhibited direct synergy against XDR-TB and an additive effect against M. tuberculosis H37Rv. DNF-3 displayed a long post-antibiotic effect (PAE) that was comparable with rifampicin but was superior to isoniazid, streptomycin and ethambutol. Importantly, DNF-3 showed no cytotoxicity to any cell line tested, with a selectivity index (SI) of >32. DNF-3 was also active against 27 nontuberculous mycobacteria (NTM) strains, Staphylococcus spp. and Streptococcus spp. Taken together, these results indicate that DNF-3 is a promising new candidate drug for treating TB. Further studies are warranted to establish the in vivo effect and therapeutic potential of DNF-3.

KEYWORDS:

DNF-3; Extensively drug-resistant; MDR/XDR-TB; Multidrug-resistant; Mycobacterium tuberculosis; NTM

[Indexed for MEDLINE]

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