New selective cyclooxygenase-2 inhibitors from cyclocoumarol: Synthesis, characterization, biological evaluation and molecular modeling

作者：Rayar Anita Marie; Lagarde Nathalie; Martin Frederique; Blanchard Florent; Liagre Bertrand; Ferroud Clotilde; Zagury Jean Francois; Montes Matthieu; Veitia Maite Sylla Iyarreta^*

来源：European Journal of Medicinal Chemistry, 2018, 146: 577-587.

DOI：10.1016/j.ejmech.2018.01.054

• Anti-inflammatory
• COX-2 inhibitors
• COX-1/COX-2 inhibition
• Cyclocoumarol
• Cyclooxygenase
• Docking study

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.

• 出版日期2018-2-25