Rayar Anita Marie, Lagarde Nathalie, Martin Frederique, Blanchard Florent, Liagre Bertrand, Ferroud Clotilde, Zagury Jean-François, Montes Matthieu, Sylla-Iyarreta Veitía Maité
Equipe 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.
Laboratoire Génétique Bioinformatique et Applications, EA 4627, Conservatoire National des Arts et Métiers, 2 rue Conté, 75003 Paris, France.
Eur J Med Chem. 2018 Feb 25;146:577-587. doi: 10.1016/j.ejmech.2018.01.054. Epub 2018 Jan 31.
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 PGE production. Among them, compound 5d exhibited the most potent inhibitory activity with a PGE 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.
在本研究中，设计、合成、表征了一系列环香豆素衍生物，并研究了它们作为COX-2选择性抑制剂的潜力。通过检测PGE生成量对所有目标化合物的抗炎活性进行了筛选。其中，化合物5d表现出最强的抑制活性，与NS-398相比，其对PGE的抑制率分别为79%和88%，并且对COX-1酶无抑制活性。对接研究表明，该化合物能够占据选择性COX-2腔，在甲氧基的氧与酶结合位点的His90和Arg513之间形成额外的氢键。
