title: 9- and 11-Substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma.
abstract: Trypanosomes from the "brucei" complex are pathogenic parasites endemic in sub-Saharan Africa and causative agents of severe diseases in humans and livestock. In order to identify new antitrypanosomal chemotypes against African trypanosomes, 4-azapaullones carrying α,β-unsaturated carbonyl chains in 9- or 11-position were synthesized employing a procedure with a Heck reaction as key step. Among the so prepared compounds, 5a and 5e proved to be potent antiparasitic agents with antitrypanosomal activity in the submicromolar range.
authors: Technische Universität Braunschweig, Institut für Medizinische und Pharmazeutische Chemie, Beethovenstraße 55, D-38106 Braunschweig, Germany.
authors: Franziska
authors: F
authors: Maiwald
authors: Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Mataojo 2020, CP 11400 Montevideo, Uruguay.
authors: Diego
authors: D
authors: Benítez
authors: Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Mataojo 2020, CP 11400 Montevideo, Uruguay.
authors: Diego
authors: D
authors: Charquero
authors: Forschungszentrum Borstel, Forschungsgruppe Infektionsimmunologie, Parkallee 22, D-23845 Borstel, Germany.
authors: Mahin Abad
authors: MA
authors: Dar
authors: Forschungszentrum Borstel, Forschungsgruppe Infektionsimmunologie, Parkallee 22, D-23845 Borstel, Germany.
authors: Hanna
authors: H
authors: Erdmann
authors: Technische Universität Braunschweig, Institut für Medizinische und Pharmazeutische Chemie, Beethovenstraße 55, D-38106 Braunschweig, Germany.
authors: Lutz
authors: L
authors: Preu
authors: Technische Universität Dortmund, Department of Chemistry and Chemical Biology, Technische Universität Dortmund, Otto-Hahn-Straße 6, 44227 Dortmund, Germany.
authors: Oliver
authors: O
authors: Koch
authors: Forschungszentrum Borstel, Forschungsgruppe Infektionsimmunologie, Parkallee 22, D-23845 Borstel, Germany.
authors: Christoph
authors: C
authors: Hölscher
authors: ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, France.
authors: Nadège
authors: N
authors: Loaëc
authors: ManRos Therapeutics, Perharidy Research Center, 29680 Roscoff, France.
authors: Laurent
authors: L
authors: Meijer
authors: Group Redox Biology of Trypanosomes, Institut Pasteur de Montevideo, Mataojo 2020, CP 11400 Montevideo, Uruguay. Electronic address: mcomini@pasteur.edu.uy.
authors: Marcelo A
authors: MA
authors: Comini
authors: Technische Universität Braunschweig, Institut für Medizinische und Pharmazeutische Chemie, Beethovenstraße 55, D-38106 Braunschweig, Germany. Electronic address: c.kunick@tu-braunschweig.de.
authors: Conrad
authors: C
authors: Kunick
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000502:physiology; D014353:Trypanosomiasis, African / Q000469:parasitology*
chemical_list: D001552:Benzazepines; D014344:Trypanocidal Agents; C547599:paullone
keywords: Chalcones; Cinnamides; Human trypanosomiasis; Nagana; Paullones; Trypanosoma brucei brucei