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New selective cyclooxygenase-2 inhibitors from cyclocoumarol: Synthesis, characterization, biological evaluation and
Anita Marie Rayar1, Nathalie Lagarde2, Frederique Martin3
1Equipe de Chimie Moléculaire du Laboratoire CMGPCE, EA 7341, Conservatoire National des Arts et métiers, 2 rue Conté, 75003, Paris, France; Laboratoire Génétique Bioinformatique et Applications, EA 4627, Conservatoire National des Arts et Métiers, 2 rue Conté, 75003 Paris, France.
Abstract:
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.
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