Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity.

ABSTRACT: Cruzain, an essential cysteine protease of the parasitic protozoan, Trypanosoma cruzi, is an important drug target for Chagas disease. We describe here a new series of reversible but time-dependent inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl heterocycles meant to provide replacements for the irreversible reactive "warheads" of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine, and vinyl-2-(N-methyl)-pyridine groups conferred reversible, time-dependent inhibition of cruzain (K_i* = 0.1-0.4 μM). These cruzain inhibitors exhibited moderate to excellent selectivity versus human cathepsins B, L, and S and showed

SUBMITTER: Chenna BC 

PROVIDER: S-EPMC7261474 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature