Antimicrobial activity of IDD-B40 against drug-resistant Mycobacterium tuberculosisopen access
- Authors
- Islam, Md Imtiazul; Seo, Hoonhee; Kim, Sukyung; Sadu, Venkata S.; Lee, Kee-In; Song, Ho-Yeon
- Issue Date
- 12-Jan-2021
- Publisher
- Nature Publishing Group
- Citation
- Scientific Reports, v.11, no.1, pp 1 - 9
- Pages
- 9
- Journal Title
- Scientific Reports
- Volume
- 11
- Number
- 1
- Start Page
- 1
- End Page
- 9
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/19011
- DOI
- 10.1038/s41598-020-80227-y
- ISSN
- 2045-2322
- Abstract
- The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis creates the urgency for new anti-tuberculosis drugs to improve the efficiency of current tuberculosis treatment. In the search for a new potential tuberculosis drug, we synthesized an isoindole based chemical library and screened a potential candidate with significant anti-tuberculosis activity. The compound named 2-hydroxy-4-(4-nitro-1,3-dioxoisoindolin-2-yl) benzoic acid (IDD-B40) showed strong activity against all the tested drug-susceptible and drug-resistant strains of M. tuberculosis, with the 50% minimum inhibitory concentrations (MIC50) of 0.39 mu g/ml both in culture broth and inside Raw 264.7 cells. Also, IDD-B40, in combination with rifampicin, exhibited a direct synergistic effect against both XDR and H37Rv M. tuberculosis. Besides, IDD-B40 showed a better post-antibiotic effect (PAE) than did some first-line drugs and showed no significant cytotoxicity to any cell line tested, with a selectivity index of >= 128. Although IDD-B40 showed a result similar to isoniazid in the preliminary mycolic acid inhibition assay, it did not exhibit any effect against other mycolic acid-producing nontuberculous mycobacterial strains (NTM), and different non-mycobacterial pathogenic strains, so further studies are required to confirm the mode of action of IDD-B40. Considering its results against M. tuberculosis, IDD-B40 is a potential anti-tuberculosis drug candidate. However, further studies are required to evaluate its potential in vivo effect and therapeutic potential.
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