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Novel Trisubstituted Arylidene Oxindoles with Potent Anti-Apoptotic Properties

Repasky, Paul J.
http://rave.ohiolink.edu/etdc/view?acc_num=wright1310326721

Abstract Details

2011, Master of Science (MS), Wright State University, Chemistry.
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 carbonyl of these substrates, the efficacy of arylidene oxindoles might be expected to involve a Michael attack of the cysteine sulfur onto the beta-carbon of the heterocyclic system in a Michael fashion. Furthermore, NMR investigations into the E/Z isomerization of such arylidene oxindoles were conducted which show that with few exceptions, isomerization is occurring in polar solvents, in which case it was deemed unnecessary to chromatographically separate isomers prior to screening. Finally, the anti-apoptotic properties of the designed molecules were examined with Human Jurkat T lymphoma cell apoptosis in a DNA Ladder assay.
Daniel Ketcha, PhD (Advisor)
Kenneth Turnbull, PhD (Committee Member)
Ioana Pavel, PhD (Committee Member)
89 p.
Biochemistry; Biology; Chemistry; Molecular Biology; Molecular Chemistry; Organic Chemistry
organic chemistry; oxindole; benzylidene; arylidene; caspase; caspase inhibitor; indole; small molecule; apoptosis; DNA ladder;

Recommended Citations

Citations

  • Repasky, P. J. (2011). Novel Trisubstituted Arylidene Oxindoles with Potent Anti-Apoptotic Properties [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1310326721

    APA Style (7th edition)

  • Repasky, Paul. Novel Trisubstituted Arylidene Oxindoles with Potent Anti-Apoptotic Properties. 2011. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1310326721.

    MLA Style (8th edition)

  • Repasky, Paul. "Novel Trisubstituted Arylidene Oxindoles with Potent Anti-Apoptotic Properties." Master's thesis, Wright State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1310326721

    Chicago Manual of Style (17th edition)

wright1310326721
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© 2011, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.