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,
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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 H
37R
V. Among the tested compounds, (
E)-
N′-[6-(4-hydroxypiperidin-1-yl)-11
H-indeno[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-
l-leucyl-
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 IC
50 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-11
H-indeno[1,2-
c]quinolin-11-one (
4g) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC
50 values of 0.46 and 0.68 μM, respectively, and is a potential lead compound for the discovery of anti-inflammatory drug candidates.
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