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Natural Product Inhibitors of Hsp90: Potential Leads for Drug Discovery
dc.contributor.advisor | Blagg, Brian S. J. | |
dc.contributor.author | Amolins, Michael Wayne | |
dc.date.accessioned | 2009-11-02T20:51:18Z | |
dc.date.available | 2009-11-02T20:51:18Z | |
dc.date.issued | 2009-07-09 | |
dc.date.submitted | 2009 | |
dc.identifier.other | http://dissertations.umi.com/ku:10470 | |
dc.identifier.uri | http://hdl.handle.net/1808/5582 | |
dc.description.abstract | This thesis represents a discussion of the advancements made in the area of Hsp90 therapeutics, and the development of a novel Hsp90 inhibitory scaffold of natural product origin. Through utilization of a recently reported firefly luciferase assay, our group was able to conduct a high-throughput screen that resulted in the identification of several Hsp90 inhibitors that contained a 1,4-naphthoquinone scaffold. From this, a library of naphthoquinones was synthesized. To further probe structure-activity relationships, a comparative molecular field analysis was performed, and a second generation of 1,4-naphthoquinones was developed. Although the results were promising, concerns arose regarding the nature of the scaffold itself. It is well documented that quinone-based scaffolds exert cytotoxicity through Michael reaction chemistry or redox activity. To circumvent this concern, the core scaffold was changed from a 1,4-naphthoquinone core to a structurally similar flavone. This was completed through utilization of molecular modeling and Western Blot analyses. | |
dc.format.extent | 121 pages | |
dc.language.iso | EN | |
dc.publisher | University of Kansas | |
dc.rights | This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author. | |
dc.subject | Pharmaceutical chemistry | |
dc.subject | Chemistry | |
dc.subject | Biochemistry | |
dc.subject | Organic chemistry | |
dc.subject | Cancer | |
dc.subject | Flavone | |
dc.subject | Heat shock proteins | |
dc.subject | Molecular modeling | |
dc.subject | Naphthoquinone | |
dc.subject | Neuroprotection | |
dc.title | Natural Product Inhibitors of Hsp90: Potential Leads for Drug Discovery | |
dc.type | Thesis | |
dc.contributor.cmtemember | Prisinzano, Thomas E. | |
dc.contributor.cmtemember | Malinakova, Helena C. | |
dc.thesis.degreeDiscipline | Medicinal Chemistry | |
dc.thesis.degreeLevel | M.S. | |
kusw.oastatus | na | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
kusw.bibid | 6857603 | |
dc.rights.accessrights | openAccess |
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Medicinal Chemistry Dissertations and Theses [80]
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Theses [4088]