9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma.

Franziska Maiwald (1) , Diego Benítez (2) , Diego Charquero (2) , Mahin Abad Dar (3) , Hanna Erdmann (3) , Lutz Preu (1) , Oliver Koch (4) , Christoph Hölscher (3) , Nadège Loaëc (5) , Laurent Meijer (5) , Marcelo A Comini (2) , Conrad Kunick (1)

1 Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig]
2 Institut Pasteur de Montevideo
3 Forschungszentrum Borstel - Research Center Borstel
4 TU - Technische Universität Dortmund [Dortmund]
5 ManRos Therapeutics

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.

Mots clés: Trypanosoma brucei brucei; Paullones; Nagana; Cinnamides; Human trypanosomiasis; Chalcones

Domaines: Biochimie, Biologie Moléculaire

Franziska Maiwald, Diego Benítez, Diego Charquero, Mahin Abad Dar, Hanna Erdmann, et al.. 9- and 11-substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma.. European Journal of Medicinal Chemistry, 2014, 83, pp.274-283. ⟨10.1016/j.ejmech.2014.06.020⟩. ⟨hal-01109648⟩