title: Nitro-, Azo-, and Amino Derivatives of Ebselen: Synthesis, Structure, and Cytoprotective Effects.
abstract: Novel azo-bis-ebselen compounds 7 were prepared by reduction of 7-nitro-2-aryl-1,2-benzisoselenazol-3(2H)-ones 3 and 6 with sodium benzenetellurolate, NaTeC6H5, and by reaction of 2-bromo-3-nitrobenzamides with Na2Se2. The X-ray structure of 7b showed that the molecule, due to strong intramolecular secondary Se···N interactions, is completely planar. Azo-compounds 7 upon further reaction with NaTeC6H5were reductively cleaved to provide 2 equiv of the corresponding aromatic amine. The weak Se-N bond was not stable enough to survive the reaction conditions, and diselenides 8 were isolated after workup. Whereas azo-bis-ebselens 7 were poor mimics of the glutathione peroxidase (GPx)-enzymes, nitroebselens 3, 6, and 11b and diselenides 8 were 3-6-fold more active than ebselen. Based on77Se NMR spectroscopy, a catalytic cycle for diselenide 8b, involving aminoebselen 14, was proposed. As assessed by chemiluminescence measurements, the good GPx-mimics could reduce production of reactive oxygen species (ROS) in stimulated human mononuclear cells more efficiently than Trolox. No toxic effects of the compounds were seen in MC3T3-cells at 25 μM.
authors.affiliation: Department of Chemistry-BMC, Uppsala University , Box 576, SE-751 23 Uppsala, Sweden.
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Singh
authors.affiliation: Department of Chemistry-BMC, Uppsala University , Box 576, SE-751 23 Uppsala, Sweden.
authors.forename: Jia-Fei
authors.initials: JF
authors.lastname: Poon
authors.affiliation: Department of Chemistry-BMC, Uppsala University , Box 576, SE-751 23 Uppsala, Sweden.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Yan
authors.affiliation: Division of Applied Materials Science, Department of Engineering Sciences, Uppsala University , Uppsala, Sweden.
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.affiliation: Division of Applied Materials Science, Department of Engineering Sciences, Uppsala University , Uppsala, Sweden.
authors.forename: Marjam Karlsson
authors.initials: MK
authors.lastname: Ott
authors.affiliation: Department of Chemistry, Howard University , Washington, D.C. 20059, United States.
authors.forename: Ray J
authors.initials: RJ
authors.lastname: Butcher
authors.affiliation: University of Bristol , School of Chemistry, Bristol, BS8 1TS, United Kingdom.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gates
authors.affiliation: Department of Chemistry-BMC, Uppsala University , Box 576, SE-751 23 Uppsala, Sweden.
authors.forename: Lars
authors.identifier: 0000-0001-7751-629X
authors.initials: L
authors.lastname: Engman
mesh_terms: D000818:Animals; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D019610:Cytoprotection / Q000187:drug effects; D054833:Isoindoles; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; C042986:ebselen