The design, synthesis, and evaluation of simplified, function-oriented analogs of the daphnane diterpene orthoesters and the laulimalides
Abstract/Contents
- Abstract
- In this work, a function-oriented array of simplified analogs of the daphnane diterpene orthoester class of natural products bearing palmitate, phenyl, or phenylacetyl orthoesters was synthesized starting from commerically available starting materials via a key late stage common diversification intermediate. These families of novel compounds were evaluated for both selective PKC activation and growth inhibition of K562 (myleogenous leukemia) cancer cells. While these analogs showed no growth inhibitory activity in K562 cells up to concentrations of 10 micromolar, they did display varying profiles of PKC activation. One analog in particular demonstrated the ability to activate and cause translocation of conventional PKC b1 and novel PKC d to the same extent as resiniferonol, a potent natural resiniferonoid. A second analog, however, was found to activate novel PKC d selectively over conventional PKC b1; surprisingly, resiniferonol did not share this selectivity profile. Because the simplified, functional analogs synthesized in this study were shown to activate PKC while having no growth inhibitory activity, these compounds should be further investigated for their potential as therapeutic leads for the treatment of diseases like Alzheimer's or Parkinson's, in which (selective) activation of PKC could serve a therapeutic purpose without being plagued by growth inhibitory pathways.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Cardin, Nathan Benjamin | |
|---|---|---|
| Associated with | Stanford University, Department of Chemistry | |
| Primary advisor | Wender, Paul A | |
| Thesis advisor | Wender, Paul A | |
| Thesis advisor | Du Bois, Justin | |
| Thesis advisor | Kanan, Matthew William, 1978- | |
| Advisor | Du Bois, Justin | |
| Advisor | Kanan, Matthew William, 1978- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Nathan Benjamin Cardin. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Nathan Benjamin Cardin
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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