Open Access. Powered by Scholars. Published by Universities.®
Physical Sciences and Mathematics Commons™
Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Physical Sciences and Mathematics
Synthesis Of Isatin Derivatives Used For The Inhibition Of Pro-Apoptotic Jurkat T Cells, Charles Michael Clay
Synthesis Of Isatin Derivatives Used For The Inhibition Of Pro-Apoptotic Jurkat T Cells, Charles Michael Clay
Browse all Theses and Dissertations
A range of substituted 1H-indole-2,3-diones (isatins) was synthesized to assess their capability to inhibit caspases and prevent apoptosis in Jurkat T cells. The key steps in the synthesis of such molecules involved electrophilic substitution of the C-5 position of the isatin nucleus (if necessary), N-alkylation, Wolff-Kishner reduction of the C-3 carbonyl group and finally, Knoevenagel condensation. The design and synthesis of such potential inhibitors was guided by SAR studies of peptide based inhibitors such as "Q-VD-O-Ph", as well as small-molecule inhibitors based upon the isatins scaffold. Previously, 3-(2,6-difluorobenzylidene)-5-nitroindolin-2-one has been shown to inhibit apoptosis in human Jurkat T cells at …
Novel Trisubstituted Arylidene Oxindoles With Potent Anti-Apoptotic Properties, Paul J. Repasky
Novel Trisubstituted Arylidene Oxindoles With Potent Anti-Apoptotic Properties, Paul J. Repasky
Browse all Theses and Dissertations
Apoptosis is a highly complex, multi-step cellular pathway utilized to initiate cell suicide. The family of enzymes largely responsible for the process is the cystienyl aspartic acid proteases (caspases). This study details the design and synthesis of a new class of small molecule caspase inhibitors, namely arylidene oxindoles, which are comparable to the isatin family of inhibitors but which offer the advantage of incorporating three points of variability into the basic scaffold. Moreover, whereas the mode of action of isatins against caspases has been demonstrated to involve nucleophilic addition of the cysteine residue of the enzymes to the C-3 ketone …