Inhibition of mitogen-activated protein kinase p38α by rooperol and analogues

dc.contributor.advisorKerwin, Sean M.
dc.contributor.authorDavis, Chelsea S.
dc.contributor.committeeMemberLewis, Karen A.
dc.contributor.committeeMemberLewis, L. Kevin
dc.date.accessioned2022-08-01T21:27:46Z
dc.date.available2022-08-01T21:27:46Z
dc.date.issued2020-08
dc.description.abstractCancer therapeutic drugs have evolved over time in correlation with the understanding of the biological mechanisms which they affect. Many anti-cancer leads have been found in natural sources. The African potato, Hypoxis hemerocallidea, is widely used in South African as a medicinal plant for the treatment of cancer and other diseases. Extracts from the corms of this plant contain the major biologically active component hypoxoside. Hypoxoside is hydrolyzed to the anti-cancer agent rooperol ((1,5-bis(3’,4’-dihydroxyphenyl) pent-1-en-4-yne) which has been shown to inhibit cancer cell lines. In a Phase I clinical trial, lung cancer patients showed promising anticancer activity results, with one patient cancer free after 5 years. Rooperol is metabolized into biologically inactive forms with glucuronic acid and sulfates groups. Analogues of rooperol have been synthesized with the goal of increasing metabolic stability while preserving anti-cancer activity. Rooperol has been seen to inhibit microtubule formation as well as inhibit mitogen-activated protein kinase p38α which is known to influence control of the cell cycle, inflammation, and cancer. The goal of this research was to investigate the ability of rooperol and analogues to inhibit p38α. The study used in vitro ELISA and luminescent ADP assay to quantify kinase activity. Then in silico docking studies were done to compare analogues and rooperol in binding to p38α. With this docking information in correlation with cytotoxicity to identify possible anti-cancer or anti-inflammatory compounds.
dc.description.departmentChemistry and Biochemistry
dc.formatText
dc.format.extent74 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationDavis, C. S. (2020). <i>Inhibition of mitogen-activated protein kinase p38α by rooperol and analogues</i> (Unpublished thesis). Texas State University, San Marcos, Texas.
dc.identifier.urihttps://hdl.handle.net/10877/16015
dc.language.isoen
dc.subjectNatural products
dc.subjectKinase inhibitors
dc.subjectRooperol
dc.subjectp38α
dc.titleInhibition of mitogen-activated protein kinase p38α by rooperol and analogues
dc.typeThesis
thesis.degree.departmentChemistry and Biochemistry
thesis.degree.disciplineBiochemistry
thesis.degree.grantorTexas State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
DAVIS-THESIS-2020.pdf
Size:
5.28 MB
Format:
Adobe Portable Document Format

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
LICENSE.txt
Size:
2.97 KB
Format:
Plain Text
Description: