Tetrahydroisoquinolines: New Inhibitors of Neutrophil Extracellular Trap (NET) Formation. (31st March 2017)

• Record Type: Journal Article
• Authors: Martinez, Nancy E.; Zimmermann, Tobias J.; Goosmann, Christian; Alexander, Tobias; Hedberg, Christian; Ziegler, Slava; Zychlinsky, Arturo; Waldmann, Herbert
• Is Part Of: Chembiochem. Volume 18:Number 10(2017)
• Page Start: 888
• Page End: 893
• Publication Date: 2017-03-31
• Subjects: inhibitors -- NETosis -- neutrophil extracellular traps (NETs) -- structure–activity relationships -- tetrahydroisoquinolines; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600650
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Neutrophils are short‐lived leukocytes that migrate to sites of infection as part of the acute immune response, where they phagocytose, degranulate, and form neutrophil extracellular traps (NETs). During NET formation, the nuclear lobules of neutrophils disappear and the chromatin expands and, accessorized with neutrophilic granule proteins, is expelled. NETs can be pathogenic in, for example, sepsis, cancer, and autoimmune and cardiovascular diseases. Therefore, the identification of inhibitors of NET formation is of great interest. Screening of a focused library of natural‐product‐inspired compounds by using a previously validated phenotypic NET assay identified a group of tetrahydroisoquinolines as new NET formation inhibitors. This compound class opens up new avenues for the study of cellular death through NET formation (NETosis) at different stages, and might inspire new medicinal chemistry programs aimed at NET‐dependent diseases. Abstract : Targ(N)ETing the traps : During infection, neutrophils expel neutrophil extracellular traps (NETs) of cellular material to fish out pathogens. Overproduction of these NETs is linked to several diseases, and suppression of NET generation is of great interest. Here we report on the identification of tetrahydroisoquinolines as new inhibitors of NET formation.