New selective cyclooxygenase-2 inhibitors from cyclocoumarol: Synthesis, characterization, biological evaluation and molecular modeling
| Autor: | Anita Marie Rayar, Florent Blanchard, Matthieu Montes, Maité Sylla-Iyarreta Veitía, Nathalie Lagarde, Jean-François Zagury, Clotilde Ferroud, Bertrand Liagre, Frederique Martin |
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| Přispěvatelé: | Laboratoire de Chimie moléculaire, génie des procédés chimiques et énergétiques (CMGPCE), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Laboratoire génomique, bioinformatique et applications (GBA), PEIRENE (PEIRENE), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre Resource Autisme Bourgogne, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Chimie des Substances Naturelles (LCSN), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Lille, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'enseignement Cnam Paris (CNAM Paris) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry medicine.drug_class chemistry.chemical_element [CHIM.THER]Chemical Sciences/Medicinal Chemistry 01 natural sciences Oxygen Anti-inflammatory Structure-Activity Relationship Drug Discovery medicine [CHIM]Chemical Sciences Binding site ComputingMilieux_MISCELLANEOUS Pharmacology chemistry.chemical_classification biology Cyclooxygenase 2 Inhibitors Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Hydrogen bond [CHIM.ORGA]Chemical Sciences/Organic chemistry Organic Chemistry General Medicine 4-Hydroxycoumarins 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme chemistry Docking (molecular) Cyclooxygenase 2 biology.protein Cyclooxygenase [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] |
| Zdroj: | European Journal of Medicinal Chemistry European Journal of Medicinal Chemistry, Elsevier, 2018, 146, pp.577-587. ⟨10.1016/j.ejmech.2018.01.054⟩ |
| ISSN: | 0223-5234 1768-3254 |
| DOI: | 10.1016/j.ejmech.2018.01.054⟩ |
| Popis: | International audience; In this work, a serie of cyclocoumarol derivatives was designed, synthesized, characterized and studied for their potentialities as selective inhibitors of COX-2. All target compounds have been screened for their anti-inflammatory activity by the assay of PGE2 production. Among them, compound 5d exhibited the most potent inhibitory activity with a PGE2 inhibition compared to NS-398 (79% and 88% respectively) and showed non-inhibitory activity towards the COX-1 enzyme. Docking studies revealed the capacity of this compound to occupy the selective COX-2 cavity establishing additional hydrogen bonds between the oxygen of the methoxy group and the His90 and Arg513 of the binding site of the enzyme. |
| Databáze: | OpenAIRE |
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