Chenna, Bala C.; Li, Linfeng; Mellott, Drake M.; Zhai, Xiang; Siqueira-Neto, Jair L.; Calvet Alvarez, Claudia; Bernatchez, Jean A.; Desormeaux, Emily; Alvarez Hernandez, Elizabeth; Gomez, Jana; McKerrow, James H.; Cruz-Reyes, Jorge; Meek, Thomas D. published the artcile< Peptidomimetic vinyl heterocyclic inhibitors of cruzain effect antitrypanosomal activity>, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is peptidomimetic vinyl heterocyclic inhibitor cruzain preparation antitrypanosomal structure activity; PVHI cruzain substrate dipeptide enzyme kinetic mol docking; drug design computer assisted; Wittig reaction Horner Wadsworth Emmons amino acid peptide coupling.
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 (Ki* = 0.1-0.4μM). These cruzain inhibitors exhibited moderate to excellent selectivity vs. human cathepsins B, L, and S and showed no apparent toxicity to human cells but were effective in cell cultures of Trypanosoma brucei brucei (EC50 = 1-15μM) and eliminated T. cruzi in infected murine cardiomyoblasts (EC50 = 5-8μM). PVHIs represent a new class of cruzain inhibitors that could progress to viable candidate compounds to treat Chagas disease and human sleeping sickness.
Journal of Medicinal Chemistry published new progress about Chagas disease. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Safety of (9Z,12Z)-Methyl octadeca-9,12-dienoate.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics