Naphthofuroquinone derivatives show strong antimycobacterial activities against drug-resistant Mycobacteria

• Published in: Journal of chemotherapy (Florence) 2017-11, Vol.29 (6), p.338-343
• Main Authors: Jang, Woong Sik, Choi, Young-Sang, Kim, Sukyung, Jyoti, Md. Anirban, Seo, Hoonhee, Han, Juhye, Kim, Yong-Sik, Lyu, Jiwon, Nam, Kung-Woo, Lee, Byung-Eui, Lee, Kee-In, Song, Ho-Yeon
• Format: Article
• Language: English
• Subjects: Antitubercular Agents - pharmacology; Cells, Cultured; Humans; Intracellular killing activity; MDR; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Naphthofuroquinone; Naphthoquinones - pharmacology; Tuberculosis, Multidrug-Resistant - drug therapy; XDR
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1080/1120009X.2017.1296987

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 IC 50 value 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.