Dipeptidyl nitrile derivatives suppress the Trypanosoma cruzi in vitro infection.

Dipeptidyl nitrile derivatives suppress the Trypanosoma cruzi in vitro infection. Exp Parasitol. 2020 Oct 30;:108032 Authors: Quilles JC, Shamim A, Tezuka DY, Batista PHJ, Lopes CD, de Albuquerque S, Montanari CA, Leitão A Abstract Chagas disease affects several countries around the world with health and sanitation problems. Cysteine proteases are essential for the virulence and replication of the Trypanosoma cruzi, being modulated by dipeptidyl nitriles and derivatives. Here, four dipeptidyl nitrile derivatives were assayed in three T. cruzi morphologies and two strains (Tulahuen and Y) using a set of assays: (i) analysis of the inhibitory activity against cysteine proteases; (ii) determination of the cytotoxic activity and selectivity index; (iii) verification of the inhibition of the trypomastigote invasion in the host cell. These compounds could inhibit the activity of cysteine proteases using the selective substrate Z-FR-MCA for the trypomastigote lysate and extracellular amastigotes. Interestingly, these compounds did not present relevant enzymatic inhibition for the epimastigote lysate. Most of the substances were also cytotoxic and selective against the trypomastigotes and intracellular amastigotes. The best compound of the series (Neq0662) could reduce the enzymatic activity of the cysteine proteases for the trypomastigotes and amastigotes. It was equipotent to the benznidazole drug in the cytotoxic studies using these two ...
Source: Experimental Parasitology - Category: Parasitology Authors: Tags: Exp Parasitol Source Type: research