title: Synthesis and evaluation of new indole-based chalcones as potential antiinflammatory agents.
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 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.
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey. Electronic address: ahmeto@anadolu.edu.tr.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Özdemir
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Mehlika Dilek
authors.initials: MD
authors.lastname: Altintop
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Gülhan
authors.initials: G
authors.lastname: Turan-Zitouni
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Biochemistry, 26470 Eskişehir, Turkey.
authors.forename: Gülşen Akalın
authors.initials: GA
authors.lastname: Çiftçi
authors.affiliation: Eskisehir Osmangazi University, Faculty of Medicine, Department of Medical Biochemistry, 26480 Eskişehir, Turkey.
authors.forename: İpek
authors.initials: İ
authors.lastname: Ertorun
authors.affiliation: Eskisehir Osmangazi University, Faculty of Medicine, Department of Medical Biochemistry, 26480 Eskişehir, Turkey.
authors.forename: Özkan
authors.initials: Ö
authors.lastname: Alataş
authors.affiliation: Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 26470 Eskişehir, Turkey.
authors.forename: Zafer Asim
authors.initials: ZA
authors.lastname: Kaplancikli
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D007211:Indoles / Q000737:chemistry*; D015227:Lipid Peroxidation / Q000187:drug effects; D008111:Liver Function Tests; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy / Q000201:enzymology
chemical_list: D047188:Chalcones; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D008565:Membrane Proteins; C030374:indole; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse
keywords: Chalcone; Cyclooxygenase; Indole