title: Synthesis of phenylpiperazine derivatives of 1,4-benzodioxan as selective COX-2 inhibitors and anti-inflammatory agents.
abstract: 1-((2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)methyl)-4-substituted-phenylpiperazine moiety was prepared and has been found to be a new and selective ligand for the enzyme cyclooxygenase-2 (COX-2). The biological activity of compound 3k as anti-inflammatory agent was further investigated both in vitro and in vivo. Notably, compound 3k exhibited the best anti-inflammatory activity among the eleven designed compounds with no toxicity, as determined by the ulcerogenic activity. Computational docking studies also showed that compound 3k has interaction with COX-2 key residues in the active site. Compound 3k maybe a new anti-inflammatory lead-candidate as powerful and novel non-ulcerogenic.
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, China.
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, China.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Sheng
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Lian
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, China.
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002351:Carrageenan; D020134:Catalytic Domain / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004146:Dioxanes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004146:Dioxanes; D010879:Piperazines; D002351:Carrageenan; D051546:Cyclooxygenase 2; C031503:phenylpiperazine; C527681:1,4-benzodioxan
keywords: 1,4-Benzodioxan; Anti-inflammatory scaffold; Cyclooxygenase-2; Phenylpiperazine