Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors

Nicole Bechmann; Torsten Kniess; Martin Köckerling; Arne Pigorsch; Jörg Steinbach; Jens Pietzsch

doi:10.1016/j.bmcl.2015.05.059

Novel (pyrazolyl)benzenesulfonamides with a nitric oxide-releasing moiety as selective cyclooxygenase-2 inhibitors

Bioorg Med Chem Lett. 2015 Aug 15;25(16):3295-300. doi: 10.1016/j.bmcl.2015.05.059. Epub 2015 May 29.

Authors

Nicole Bechmann¹, Torsten Kniess², Martin Köckerling³, Arne Pigorsch³, Jörg Steinbach¹, Jens Pietzsch⁴

Affiliations

¹ 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.
² Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Bautzner Landstrasse 400, 01328 Dresden, Germany.
³ University of Rostock, Institute of Chemistry, Inorganic Solid State Chemistry, 18059 Rostock, Germany.
⁴ 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.

PMID: 26081289
DOI: 10.1016/j.bmcl.2015.05.059

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.

Keywords: Anti-inflammatory therapy; Cardiovascular side effects; Celecoxib; Direct/indirect NO coupling; Griess assay; Organic nitrate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Benzenesulfonamides
Cardiovascular Diseases / chemically induced
Cyclooxygenase 2 Inhibitors / chemical synthesis
Cyclooxygenase 2 Inhibitors / chemistry
Cyclooxygenase 2 Inhibitors / pharmacology
Enzyme Activation / drug effects
Humans
Inhibitory Concentration 50
Molecular Structure
Nitric Oxide / metabolism*
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase 2 Inhibitors
Sulfonamides
Nitric Oxide