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- Title
Discovery of Indeno[1,2-c]quinoline Derivatives as Potent Dual Antituberculosis and Anti-Inflammatory Agents.
- Authors
Chih-Hua Tseng; Chun-Wei Tung; Chen-Hsin Wu; Cherng-Chyi Tzeng; Yen-Hsu Chen; Tsong-Long Hwang; Yeh-Long Chen
- Abstract
A series of indeno[1,2-c]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H37RV. Among the tested compounds, (E)-N'-[6-(4-hydroxypiperidin-1-yl)-11Hindeno[ 1,2-c]quinolin-11-ylidene]isonicotino-hydrazide (12), exhibited significant activities against the growth of M. tuberculosis (MIC values of 0.96 μg/mL) with a potency approximately equal to that of isoniazid (INH), an anti-TB drug. Important structure features were analyzed by quantitative structure-activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the anti-TB activity. The anti-inflammatory activity was induced by superoxide anion generation and neutrophil elastase (NE) release using the formyl-L-methionyl-Lleucyl- L-phenylalanine (fMLF)-activated human neutrophils method. Results indicated that compound 12 demonstrated a potent dual inhibitory effect on NE release and superoxide anion generation with IC50 values of 1.76 and 1.72 μM, respectively. Our results indicated that compound 12 is a potential lead compound for the discovery of dual anti-TB and anti-inflammatory drug candidates. In addition, 6-[3-(hydroxymethyl)piperidin-1-yl]-9-methoxy-11H- indeno[1,2-c]quinolin-11-one (4g) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC50 values of 0.46 and 0.68 μM, respectively, and is a potential lead compound for the discovery of anti-inflammatory drug candidates.
- Subjects
QUINOLINE derivatives; ANTI-inflammatory agents; NEUTROPHILS; ISONIAZID; QSAR models
- Publication
Molecules, 2017, Vol 22, Issue 6, p1001
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules22061001