Document Type: Short communication
Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance, Johann Wolfgang Goethe-University Frankfurt, Max-von-Laue-Straße 7, D-60438 Frankfurt am Main, Germany
Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4051 Basel, Switzerland
A set of conformationally restricted analogues of the natural product primin were synthesized as potential antiprotozoal agents. The synthesis utilizes quinone C-H functionalization methods to enable an efficient and easy access to primin analogues. The antiprotozoal activities of this series were evaluated in a panel of parasites and compared with the natural product primin. For all synthesized primin analogues a potent in vitro activity was found against the pathogen Trypanosoma brucei rhodesiense (IC50 < 0.05 µg/mL). The observed antiprotozoal activity is not related to production of reactive oxygen species (ROS). Initial results of the in vivo experiments with a T. b. rhodesiense rodent animal model of the human disease were also reported. Intraperitoneal injection administration of compound 7 resulted in complete clearance of T. b. rhodesiense in tested rodent animals 24 hours after the last treatment. Our results show that the primin scaffold represents a new scaffold for further development of potent inhibitors of Trypanosoma brucei rhodesiense.