title: Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives.
abstract: Design, synthesis and pharmacological activities of a group of 1,3,5-trisubstituted pyrazolines were reported. The chemical structures of the synthesized compounds have been assigned on the basis of IR, MS, (1)H NMR, and (13)C NMR spectral analyses. The synthesized 1,3,5-trisubstituted pyrazoline derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 4h, 6e, 7a, 7e, and 9 showed more potent anti-inflammatory and analgesic activities than the reference drug celecoxib. On the basis of their higher activities in the in vivo studies compared with celecoxib, the five compounds 4h, 6e, 7a, 7e and 9 were selected to test their inhibitory activities against ovine COX-1/2 using an in vitro cyclooxygenase inhibition assay. Docking study of compounds 7a, 7e and 9 into the COX-2 binding site revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors.forename: Maged A
authors.initials: MA
authors.lastname: Abdel-Sayed
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors.forename: Said M
authors.initials: SM
authors.lastname: Bayomi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt.
authors.forename: Magda A
authors.initials: MA
authors.lastname: El-Sherbeny
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors.forename: Naglaa I
authors.initials: NI
authors.lastname: Abdel-Aziz
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 Pharmacology, Faculty of Pharmacy, University of Mansourua, Mansoura 35516, Egypt.
authors.forename: George S G
authors.initials: GS
authors.lastname: Shehatou
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: alaa_moenes@yahoo.com.
authors.forename: Alaa A-M
authors.initials: AA
authors.lastname: Abdel-Aziz
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051545:Cyclooxygenase 1
keywords: Anti-inflammatory activity; Molecular docking study; Pyrazoline derivatives; Selective COX-2 inhibition