title: Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors.
abstract: Inhibition of cyclooxygenase-2 (COX-2) is a promising anti-inflammatory therapeutic strategy, but long-term medication with COX-2-inhibitors (coxibs) may be associated with adverse cardiovascular effects. Functionalization of existing lead structures with nitric oxide (NO)-releasing moieties is an auspicious approach to minimize these effects. In this regard, an organic nitrate (-O-NO2) substituent was introduced at a (pyrazolyl)benzenesulfonamide lead structure. The novel NO-coxibs selectively inhibited COX-2 in a low micromolar range (IC50(COX-2): 0.22-1.27 μM) and are supposed to be promising anti-inflammatory compounds with, in parallel, positive effects on vascular homeostasis.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Bautzner Landstrasse 400, 01328 Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, 01069 Dresden, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bechmann
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Kniess
authors.affiliation: University of Rostock, Institute of Chemistry, Inorganic Solid State Chemistry, 18059 Rostock, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Köckerling
authors.affiliation: University of Rostock, Institute of Chemistry, Inorganic Solid State Chemistry, 18059 Rostock, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Pigorsch
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Bautzner Landstrasse 400, 01328 Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, 01069 Dresden, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Bautzner Landstrasse 400, 01328 Dresden, Germany; Technische Universität Dresden, Department of Chemistry and Food Chemistry, 01069 Dresden, Germany. Electronic address: j.pietzsch@hzdr.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000139:chemically induced; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D009569:Nitric Oxide; D013449:Sulfonamides; D000096926:Benzenesulfonamides
keywords: Anti-inflammatory therapy; Cardiovascular side effects; Celecoxib; Direct/indirect NO coupling; Griess assay; Organic nitrate