Chagas disease is a health and sanitation endemic issue in the South America, promoted by the protozoa from Trypanosoma cruzi. However, such disease has spread around the world and affected numerous countries. One of the most relevant targets for the parasite and, consequently, for the disease development are the Cysteine proteases. These enzymes are essential for the parasite life cycle and replication, and protease inhibitors, such as dipeptidyl nitriles and their derivatives, might bring positive effects and emerge as drug candidates In this work, four dipeptidyl nitrile derivatives (Neq 0594, 0666, 0662 and 0663) were assayed against the three T. cruzi morphologies and two strains (Y and Tulahuen). All the inhibitors were able to inhibit the in vivo cysteine proteases activity in the amastigote form. Besides that, Neq0662 promoted significant proteolytic activity suppression for infective and replicative morphologies. In addition, it was equipotent to the reference drug (benznidazole) in the cytotoxic studies, besides being. selective for the parasite, with parasite invasion inhibition of the mammalian host cell in all conditions tested. The results indicate that these class of compounds are promising as drug candidates due to their relevant bioactive profile comparing to the reference drug.
Dr. Pedro Henrique Jatai Batista is an analyst at Lasa-Dosage Laboratory Research in Campinas/SP, Brazil. Pedro was born in Fortaleza, Ceará-Brazil and completed his Ph. D in Biological Chemistry (2019) at the Chemistry Institute of São Carlos, University of São Paulo (USP), Brazil, which his thesis was based on the development and validation of methods for bioactivity compounds analysis, as well as their metabolites, by HPLC-DAD-MS. During his academic life, he got opportunities to work with different analytical tools, as chromatographic and spectrometric analysis for natural compounds, project developed during his Master degree in Organic Chemistry at Federal University of Ceará (UFC), Brazil. Besides acquiring expertise about analytical procedures, he was able to improve his knowledge on medicinal chemistry, focused on enzyme inhibition and cellular evaluation. Currently, Pedro he has taken a position at Lasa-Dosage Laboratory Research in Campinas, São Paulo, as an analyst on regulatory affairs.