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


ÖZDEMİR A., ALTINTOP M. D., Turan-Zitouni G., AKALIN ÇİFTÇİ G., Ertorun I., Alatas O., ...More

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.89, pp.304-309, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 89
  • Publication Date: 2015
  • Doi Number: 10.1016/j.ejmech.2014.10.056
  • Journal Name: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.304-309
  • Keywords: Chalcone, Indole, Cyclooxygenase, BIOLOGICAL EVALUATION, NITRIC-OXIDE, INHIBITORS SYNTHESIS, COX-2 INHIBITORS, DERIVATIVES, CYCLOOXYGENASE, INDOMETHACIN, DESIGN, SEPSIS, DOCKING
  • Eskisehir Osmangazi University Affiliated: Yes

Abstract

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 mu g/mL, COX-2 IC50 = 9.5 +/- 0.8 mu g/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 mu g/mL). According to in vivo studies, these compounds also displayed antiinflammatory and antioxidant activities. (C) 2014 Elsevier Masson SAS. All rights reserved.