Synthesis and evaluation of new indole-based chalcones as potential antiinflammatory agents

In the present work, new indole-based chalcone derivatives were obtained via the reaction of 5-substituted-1H-indole-3-carboxaldehydes/1-methylindole-3-carboxaldehyde with appropriate acetophenones. The synthesized compounds were investigated for their in vitro COX-1 and COX-2 inhibitory activity. T...

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Published in:European journal of medicinal chemistry 2015-01, Vol.89, p.304-309
Main Authors: Özdemir, Ahmet, Altıntop, Mehlika Dilek, Turan-Zitouni, Gülhan, Çiftçi, Gülşen Akalın, Ertorun, İpek, Alataş, Özkan, Kaplancıklı, Zafer Asım
Format: Article
Language:English
Subjects:
Animals
Cell Survival - drug effects
Chalcone
Chalcones - chemical synthesis
Chalcones - chemistry
Chalcones - pharmacology
Chalcones - therapeutic use
Cyclooxygenase
Cyclooxygenase 1 - metabolism
Cyclooxygenase 2 - metabolism
Cyclooxygenase Inhibitors - chemical synthesis
Cyclooxygenase Inhibitors - chemistry
Cyclooxygenase Inhibitors - pharmacology
Cyclooxygenase Inhibitors - therapeutic use
Disease Models, Animal
Drug Design
Drug Evaluation, Preclinical
Indole
Indoles - chemistry
Lipid Peroxidation - drug effects
Liver Function Tests
Membrane Proteins - metabolism
Mice
Molecular Structure
NIH 3T3 Cells
Oxidative Stress - drug effects
Sepsis - drug therapy
Sepsis - enzymology
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Summary:In the present work, new indole-based chalcone derivatives were obtained via the reaction of 5-substituted-1H-indole-3-carboxaldehydes/1-methylindole-3-carboxaldehyde with appropriate acetophenones. The synthesized compounds were investigated for their in vitro COX-1 and COX-2 inhibitory activity. The most effective COX inhibitors were also evaluated for their in vivo antiinflammatory and antioxidant activities in LPS induced sepsis model. Furthermore, the CCK-8 assay was carried out to determine cytotoxic effects of all compounds against NIH/3T3 mouse embryonic fibroblast cells. 3-(5-Bromo-1H-indol-3-yl)-1-(4-cyanophenyl)prop-2-en-1-one (6) can be considered as a non-selective COX inhibitor (COX-1 IC50 = 8.1 ± 0.2 μg/mL, COX-2 IC50 = 9.5 ± 0.8 μg/mL), whereas 3-(5-methoxy-1H-indol-3-yl)-1-(4-(methylsulfonyl)phenyl)prop-2-en-1-one (1) inhibited only COX-1 (IC50 = 8.6 ± 0.1 μg/mL). According to in vivo studies, these compounds also displayed antiinflammatory and antioxidant activities. New indole-based chalcones were synthesized and tested for in vitro COX-1 and COX-2 inhibitory activity. The most effective COX inhibitors were evaluated for their in vivo antiinflammatory and antioxidant effects. [Display omitted] •New indole-based chalcone derivatives were synthesized.•The compounds were tested in vitro COX-1 and COX-2 inhibitory activity.•Compounds 1 and 6 were the most effective COX inhibitors.•Compounds 1 and 6 were evaluated for antiinflammatory and antioxidant effects.•Compounds 1 and 6 showed in vivo antiinflammatory and antioxidant activity.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2014.10.056