Design, Synthesis, and Testing of Antiprotozoal Activity of Primin and Analogues

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 to the natural product primin. for all the 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 the 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 the 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.