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

•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.

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.

Graphical abstractNew 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.Figure optionsDownload full-size imageDownload as PowerPoint slide