title: Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies.
abstract: The design, synthesis and pharmacological activities of a group of 5,5-diphenylimidazolidine-2,4-dione bearing anilide, phenacyl and benzylidene fragments 2-27 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 14 showed 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.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: alaa_moenes@yahoo.com.
authors.forename: Alaa A-M
authors.initials: AA
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
authors.forename: Adel S
authors.initials: AS
authors.lastname: El-Azab
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Laila A
authors.initials: LA
authors.lastname: Abou-Zeid
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Kamal Eldin H
authors.initials: KE
authors.lastname: ElTahir
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Naglaa I
authors.initials: NI
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
authors.forename: Rezk R
authors.initials: RR
authors.lastname: Ayyad
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulrahman M
authors.initials: AM
authors.lastname: Al-Obaid
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000813:Anilides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D048289:Imidazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010147:Pain Measurement / Q000187:drug effects; D010672:Phenytoin; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D048289:Imidazolidines; D008024:Ligands; D010672:Phenytoin; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory activity; COX-1/2 inhibition; Imidazolidine-2,4-dione; Molecular docking study; Synthesis