Author

David Jackson

Date of Award

2013

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Committee Chair

William N. Setzer

Committee Member

Robert McFeeters

Committee Member

Luis R. Cruz-Vera

Subject(s)

Protein kinases, Phosphoinositides--Physiological effect, Cellular signal transduction

Abstract

PI3K (phosphoinositide 3-kinase) is responsible for a large number of signaling pathways involved in a range of conditions ranging from allergic response to tumor growth. Current research is still being done to find novel selective inhibitors for the different isoforms of PI3K. This research was performed in order to find new selective inhibitors from the world of natural products. A list of known pharmaceutical inhibitors was run in order to compare how well the natural product inhibitors performed. Eleven selective and semi-selective inhibitors were found to inhibit PI3K. The alkaloids found include berberine, chelerythine, isaindigotone, noscapine, pseudocoptisine, and tetrandrine. The flavonoids found were malvidin, pentamethoxyflavone, and vitexin. The triterpenoids found to inhibit PI3K in this experiment were ganoderic acid and oleandrin. The residues that participated in binding to the ligands were examined for trends. Promising trends were found both among binding to natural products as well as pharmaceuticals.

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