title: Synthesis of new ibuprofen derivatives with their in silico and in vitro cyclooxygenase-2 inhibitions.
abstract: Cyclooxygenase-2 (COX-2) is one of the important targets for treatment of inflammation related diseases. In the literature, most of drug candidates are first synthesized and then their COX-2 inhibitory activities are tested by in vitro and in vivo experiments. However, synthesis of dozens of drug analogues without any interpretations on their inhibitory activity can result in loss of time and chemicals. Therefore, synthetic drug designs with molecular modeling are of importance to synthesize selective drug candidates against inflammatory diseases. The synthesis of the novel ibuprofen derivatives through their in silico and in vitro COX-2 inhibitory activities were investigated in the present study. Starting from ibuprofen, ibuprofen amide and ibuprofen acyl hydrazone derivatives were synthesized. According to the results of the in silico molecular docking and in vitro enzyme inhibition studies, the synthesized novel ibuprofen derivatives have selective COX-2 inhibition, and molecule 3a and 3c were showed higher inhibition compared to ibuprofen. In conclusion, the newly synthesized ibuprofen derivatives can be used in model in vivo studies.
authors.affiliation: Dokuz Eylül University, Graduate School of Natural and Applied Sciences, Department of Chemistry, Kaynaklar Campus, 35160 İzmir, Turkey; Dokuz Eylül University, Faculty of Science, Department of Chemistry, Division of Organic Chemistry, Kaynaklar Campus, 35160 İzmir, Turkey.
authors.forename: Cevher
authors.initials: C
authors.lastname: Gundogdu-Hizliates
authors.affiliation: Dokuz Eylül University, Graduate School of Natural and Applied Sciences, Department of Chemistry, Kaynaklar Campus, 35160 İzmir, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Alyuruk
authors.affiliation: Dokuz Eylül University, Graduate School of Natural and Applied Sciences, Department of Chemistry, Kaynaklar Campus, 35160 İzmir, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gocmenturk
authors.affiliation: Dokuz Eylül University, Graduate School of Natural and Applied Sciences, Department of Chemistry, Kaynaklar Campus, 35160 İzmir, Turkey; Dokuz Eylül University, Faculty of Science, Department of Chemistry, Division of Organic Chemistry, Kaynaklar Campus, 35160 İzmir, Turkey.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Ergun
authors.affiliation: Dokuz Eylül University, Graduate School of Natural and Applied Sciences, Department of Chemistry, Kaynaklar Campus, 35160 İzmir, Turkey; Dokuz Eylül University, Faculty of Science, Department of Chemistry, Division of Biochemistry, Kaynaklar Campus, 35160 İzmir, Turkey. Electronic address: levent.cavas@deu.edu.tr.
authors.forename: Levent
authors.initials: L
authors.lastname: Cavas
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D051545:Cyclooxygenase 1 / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007052:Ibuprofen / Q000031:analogs & derivatives / Q000737:chemistry*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D007052:Ibuprofen
keywords: Cyclooxygenase-2; Ibuprofen; Molecular docking; Molecular modeling; Selective inhibitor