title: Naphthofuroquinone derivatives show strong antimycobacterial activities against drug-resistant Mycobacteria.
abstract: Tuberculosis, one of the world's major health problems, has become more serious due to the emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB). In this study, we performed three anti-MTB assays to evaluate the anti-mycobacterial activity of naphthofuroquinone derivatives against drug-resistant MTB. Among them, methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate (DFC2) exhibited strong anti-mycobacterial activity against MTB H37Ra, H37Rv and four drug-resistant MTB strains. The MIC of DFC2 ranged from 0.19-0.39 μg/ml to 0.78-1.56 μg/ml against all tested MTB strains. Moreover, DFC2 showed low cytotoxicity against fibroblast cells (L929) at concentrations 10-40-fold higher than their MICs. The IC50value of DFC2 against L929 cells was 15.218 μg/ml. In addition, DFC2 reduced the number of intracellular M. tuberculosis in macrophages in a dose-dependent manner. Taken together, our results indicate DFC2 to be promising new candidate agents for the treatment of tuberculosis.
authors.affiliation: c Regional Innovation Center , Soonchunhyang University , Asan , Korea.
authors.forename: Woong Sik
authors.initials: WS
authors.lastname: Jang
authors.affiliation: a Department of Microbiology and Immunology , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Young-Sang
authors.initials: YS
authors.lastname: Choi
authors.affiliation: a Department of Microbiology and Immunology , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Sukyung
authors.initials: S
authors.lastname: Kim
authors.affiliation: a Department of Microbiology and Immunology , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Md Anirban
authors.initials: MA
authors.lastname: Jyoti
authors.affiliation: a Department of Microbiology and Immunology , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Hoonhee
authors.initials: H
authors.lastname: Seo
authors.affiliation: a Department of Microbiology and Immunology , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Juhye
authors.initials: J
authors.lastname: Han
authors.affiliation: a Department of Microbiology and Immunology , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Yong-Sik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: b Department of Pulmonary and Critical Care Medicine , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Lyu
authors.affiliation: d Department of Life Science and Biotechnology , Soonchunhyang University , Asan , South Korea.
authors.forename: Kung-Woo
authors.initials: KW
authors.lastname: Nam
authors.affiliation: e Department of Chemistry , Soonchunhyang University , Asan , South Korea.
authors.forename: Byung-Eui
authors.initials: BE
authors.lastname: Lee
authors.affiliation: f Green Chemistry Division , Korea Research Institute of Chemical Technology , Taejon 305-600 , Korea.
authors.forename: Kee-In
authors.initials: KI
authors.lastname: Lee
authors.affiliation: a Department of Microbiology and Immunology , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.|b Department of Pulmonary and Critical Care Medicine , School of Medicine, Soonchunhyang University , Cheonan , Chungnam 330-090 , South Korea.
authors.forename: Ho-Yeon
authors.initials: HY
authors.lastname: Song
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009285:Naphthoquinones / Q000494:pharmacology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D009285:Naphthoquinones
keywords: Intracellular killing activity; MDR; Mycobacterium tuberculosis; Naphthofuroquinone; XDR