Synthesis and Evaluation of New Peptidyl-Nitriles as Trypanocidal Agents

Chagas disease is a noteworthy public health problem in Latin America. This illness is caused by the protozoan parasite, Trypanosoma cruzi. Current therapy is limited to benznidazole and nifurtimox, both of which are associated with side effects that may impair the therapy and are only effective in the acute phase of the disease.1 Therefore, the need of discovering of new therapeutic options for chronic Chagas disease remains a challenge in the field of Medicinal Chemistry.
Herein we describe the synthesis of new peptidyl nitriles which will be evaluated to determine its potency against cruzain, the main cysteine protease of T cruzi. The synthetic strategy has three key steps: a Negishi cross-coupling reaction, a diastereoselective reductive amination,2 and a peptide coupling to introduce the peptidyl-nitrile function. Both syn and anti-peptidyl-nitriles (from L and D-serine) were prepared for the biological tests. Investigations about the trypanocidal activity are underway.