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

• DOI: 10.1016/j.ejmech.2014.06.020
• Publication Date: 2014-06-11T17:13:33Z
• Authors: Franziska Maiwald; Diego Benítez; Diego Charquero; Mahin Abad Dar; Hanna Erdmann; Lutz Preu; Oliver Koch; Christoph Hölscher; Nadège Loaëc; Laurent Meijer; Marcelo A. Comini; Conrad Kunick
• Keywords: 0301 basic medicine; 0303 health sciences; Macrophages; Trypanosoma brucei brucei; Benzazepines; Trypanocidal Agents; Cell Line; 3. Good health; Mice; Structure-Activity Relationship; 03 medical and health sciences; Trypanosomiasis, African; Drug Design; Animals; Humans; Cell Proliferation

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.