title: Tetrahydroisoquinolines: New Inhibitors of Neutrophil Extracellular Trap (NET) Formation.
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.
authors.affiliation: Department of Chemical Biology, Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.|Lehrbereich Chem. Biologie, Fakultät Chemie, Technische Universität Dortmund, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany.|Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Charitéplatz 1, Campus Charité Mitte, 10117, Berlin, Germany.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Martinez
authors.affiliation: Department of Chemical Biology, Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.|Lehrbereich Chem. Biologie, Fakultät Chemie, Technische Universität Dortmund, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany.
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Zimmermann
authors.affiliation: Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Charitéplatz 1, Campus Charité Mitte, 10117, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Goosmann
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité Campus Mitte (CCM), Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Alexander
authors.affiliation: Department of Chemistry, Umeå Center for Microbial Research, Umeå University, KBC, C4, Linnaeus väg 10, 90187, Umeå, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Hedberg
authors.affiliation: Department of Chemical Biology, Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
authors.forename: Slava
authors.initials: S
authors.lastname: Ziegler
authors.affiliation: Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Charitéplatz 1, Campus Charité Mitte, 10117, Berlin, Germany.
authors.forename: Arturo
authors.initials: A
authors.lastname: Zychlinsky
authors.affiliation: Department of Chemical Biology, Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.|Lehrbereich Chem. Biologie, Fakultät Chemie, Technische Universität Dortmund, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
mesh_terms: D016923:Cell Death; D065206:Extracellular Traps / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: D044005:Tetrahydroisoquinolines
keywords: NETosis; inhibitors; neutrophil extracellular traps (NETs); structure-activity relationships; tetrahydroisoquinolines