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- Title
3,6-Dihydroxyflavone Has Antituberculosis Activity and Suppresses Lung Inflammation.
- Authors
Kwak, Chulhee; Lee, Yeongjoon; Jeon, Dasom; Durai, Prasannavenkatesh; Ryoo, Sungweon; Kim, Yangmee
- Abstract
The antimycobacterial and anti-inflammatory effects of 3,6-dihydroxyflavone (3,6- DHF), a flavonoid with anticancer and antibacterial activities, were investigated in lipopolysaccharide ( LPS)-stimulated human lung fibroblast MRC-5 cells. 3,6- DHF had antimycobacterial effects on Mycobacterium tuberculosis (Mtb) H37Rv, multidrug-resistant, and extensively drug-resistant clinical isolates with mean minimum inhibitory concentrations of 25, 100, and 100 µg/ mL, respectively. 3,6- DHF bound Mtb β-ketoacyl-acyl carrier protein synthase III ( mtKASIII) with high affinity through hydrogen bonding of 3,6- DHF of A-ring 6-hydroxyl and C-ring 3-hydroxyl groups with Tyr304 and Gly209 of mtKASIII. Comparison of 3,6- DHF and 3,6,3′,4′-tetrahydroxyflavone (3,6,3′,4′- THF) activities revealed that 3,6,3′,4′- THF did not have anti-tuberculosis ( TB) activity, implying that increased hydrophilicity decreases TB membrane permeabilization. 3,6- DHF reduced tumor necrosis factor ( TNF)-α, interleukin ( IL)-6, IL-12, IL-1β, and matrix metalloproteinase ( MMP)-1 mRNA levels and suppressed phosphorylation levels of extracellular signal-regulated kinase ( ERK) in LPS-stimulated MRC-5 cells. These data indicate that 3,6- DHF could be developed as a potential anti- TB drug, which also suppresses lung inflammation.
- Subjects
FLAVONES; PNEUMONIA treatment; ANTITUBERCULAR agents; DRUG activation; FIBROBLASTS; CLINICAL trials
- Publication
Bulletin of the Korean Chemical Society, 2017, Vol 38, Issue 8, p821
- ISSN
0253-2964
- Publication type
Article
- DOI
10.1002/bkcs.11175