Discovery of indeno[1,2-c]quinoline derivatives as potent dual antituberculosis and anti-inflammatory agents

Chih Hua Tseng, Chun Wei Tung, Chen Hsin Wu, Cherng Chyi Tzeng, Yen Hsu Chen, Tsong Long Hwang, Yeh Long Chen

Research output: Contribution to journalArticle

10 Citations (Scopus)

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)-11H-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 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.

Original languageEnglish
Article number1001
JournalMolecules
Volume22
Issue number6
DOIs
Publication statusPublished - Jun 1 2017
Externally publishedYes

Fingerprint

tuberculosis
quinoline
Leukocyte Elastase
neutrophils
Tuberculosis
Anti-Inflammatory Agents
Superoxides
Lead compounds
Derivatives
inorganic peroxides
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Inhibitory Concentration 50
lead compounds
leucyl-phenylalanine
drugs
Pharmaceutical Preparations
anions
Isoniazid
Phenylalanine

Keywords

  • Anti-inflammatory activity
  • Antimycobacterial activity
  • Indeno[1,2-c]quinoline

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Discovery of indeno[1,2-c]quinoline derivatives as potent dual antituberculosis and anti-inflammatory agents. / Tseng, Chih Hua; Tung, Chun Wei; Wu, Chen Hsin; Tzeng, Cherng Chyi; Chen, Yen Hsu; Hwang, Tsong Long; Chen, Yeh Long.

In: Molecules, Vol. 22, No. 6, 1001, 01.06.2017.

Research output: Contribution to journalArticle

Tseng, Chih Hua ; Tung, Chun Wei ; Wu, Chen Hsin ; Tzeng, Cherng Chyi ; Chen, Yen Hsu ; Hwang, Tsong Long ; Chen, Yeh Long. / Discovery of indeno[1,2-c]quinoline derivatives as potent dual antituberculosis and anti-inflammatory agents. In: Molecules. 2017 ; Vol. 22, No. 6.
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