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Date Permissions Signed

5-30-2019

Date of Award

Spring 2019

Document Type

Masters Thesis

Department or Program Affiliation

Chemistry

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

O'Neil, Gregory (Gregory W.)

Second Advisor

Vyvyan, James R.

Third Advisor

Antos, John M.

Abstract

The archazolids are a family of natural products that display powerful growth inhibitory activity against a number of human cancer cell lines. This activity has been linked to inhibition of the vacuolar-type ATPase (V-ATPase) and more recently cyclooxygenase (COX) enzymes. Using the archazolid structure as a starting point, several simplified analogues have been prepared and assayed for their V-ATPase and COX inhibitory activity. These simplified analogues were prepared using a novel Suzuki coupling with yields over 80%. They were assayed to investigate both their V-ATPase and COX inhibitory activity. In our assays there was no COX inhibition, while there was measurable V-ATPase inhibition. The V-ATPase inhibition showed an important difference between the natural product triene (ZZE) and an isomer (ZEE triene) that were synthesized.

Type

Text

Keywords

Archazolid, Organic Synthesis, Chemistry, V-ATPase, COX, Natural Product Synthesis, Complex Polyenes, Natural Product Derived Fragment

Publisher

Western Washington University

OCLC Number

1103711867

Subject – LCSH

Adenosine triphosphatase--Synthesis--Inhibitors; Cyclooxygenases--Synthesis--Inhibitors; Antineoplastic agents

Format

application/pdf

Genre/Form

masters theses

Language

English

Rights

Copying of this thesis in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this document for commercial purposes, or for financial gain, shall not be allowed without the author’s written permission.

Available for download on Wednesday, January 01, 2020

Included in

Chemistry Commons

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