Small Molecule Caspase Inhibitors using Isatin and Oxindole Scaffolds

Abstract

<p>Quinolyl-valyl-0-methylaspartyl-[2,6difluorophenoxy]-methyl ketone (Q-VD-OPh) is a next generation broad spectrum caspase inhibitor, the effectiveness and reduced toxicity of which can be partially attributable to the carboxyterminal O-phenoxy group as well as the aminoterminal quinolyl groups. We seek to incorporate some of these unique recognition elements onto small molecule, heterocyclic scaffolds such as isatins and oxindoles. Thus, isatins bearing electron withdrawing groups on C-5 and a 2,6-difluorobenzyl substituent have been prepared by analogy to the well studied N-substituted 5-pyrrololidinylsulfonyl isatins. Moreover, 3-benzylidine oxindole derivatives bearing these structural motifs have also been prepared and their effectiveness as apoptosis inhibitors was examined employing human Jurkat T cells.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 16, 2010</p>