Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies
Journal Article
Al-Obaid, laa A.-M. Abdel-Aziz, Adel S. El-Azab, Laila A. Abou-Zeid, Kamal Eldin H. ElTahir, Naglaa I. Abdel-Aziz, Rezk R. Ayyad, Abdulrahman M. . 2016
Publication Online URL:
Volume Number:
115,
Pages:
121–131
Publication Abstract:
The design, synthesis and pharmacological activities of a group of 5,5-diphenylimidazolidine-2,4-dione bearing anilide, phenacyl and benzylidene fragments2–27 were reported. The prepared 5,5-diphenylimidazolidine-2,4-dione derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 5, 9, 10, 13, and 14 showed significant and potent anti-inflammatory and analgesic activities almost equivalent to reference drug celecoxib. In COX-1/2 inhibition assay, compounds 5, 9, 10 and 14showed high COX-2 inhibitory activity (IC50 = 0.70 μM, 0.44 μM, 0.61 μM and 0.41 μM; respectively) and selectivity index (SI) range of 142–243 comparable to celecoxib [COX-2 (SI) > 333]. These potent COX-2 inhibitors 9, 10, 13, and 14 were docked into the active site pocket of COX-2 to explore the binding mode and possible interactions of these ligands.