Isolation, structure determination and total synthesis of potential cancer chemotherapeutic agents from natural sources
department or school: Science, Faculty of
department or school: Chemistry, Department of
data provider: DSpace
degree campus: UBCV
creator: Britton, Robert A.
issued: 2009-09-29T20:07:15Z
issued: 2002
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: The ultimate goal in the chemotherapeutic treatment of cancer is the development of drugs that are highly effective against tumor cells and have little or no effect on healthy cells. Key to this pursuit is the identification of differences that exist between the life cycle of normal and cancerous cells. Thus, the discovery of new small molecule inhibitors of enzymes that regulate cellular growth and division should provide a better understanding of these biological processes and perhaps lead to more selective cancer treatments. Mitosis, or cell division, is disrupted by antimitotic agents, which correspondingly have become the most promising chemotherapeutics in cancer treatment. Recently, the Caribbean soft coral Erythropodium caribaeorum was shown to be a good source of eleutherobin, a potent antimitotic agent. Having procured eleutherobin from this source, synthetic manipulations of the natural material provided a series of eleuthoside congeners, which were assayed for antimitotic activity. A remarkable relationship between the Δ[sup 2’,3’] olefin and eleuthoside biological activity was highlighted by these studies. The G2 checkpoint is one of a series of checkpoints that temporarily halt cell cycle progression in order to allow for repair of damaged DNA. It has been demonstrated in vitro that the inhibition of this checkpoint, in combination with a DNA damaging agent, selectively potentiates the killing of cancer cells. Extracts of the Brazilian ascidian Didemnum granulatum demonstrated G2 checkpoint inhibition activity. Fractionation of these extracts resulted in the isolation of isogranulatimide. In order to unambiguously confirm the structural assignment of this substance, generate sufficient material for biological testing and investigate the effect of structure on its biological activity, an efficient synthesis of isogranulatimide and several congeners was developed. Concurrently, two new analogues of okadaic acid, a potent protein phosphatase inhibitor, ha…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/13300
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note: I S O L A T I O N , S T R U C T U R E D E T E R M I N A T I O N A N D T O T A L S Y N T H E S I S OF P O T E N T I A L C A N C E R C H E M O T H E R A P E U T I C A G E N T S F R O M N A T U R A L S O U R C E S by R O B E R T A . B R I T T O N B . S c , University of Waterloo, 1996 A THESIS S U B M I T T E D IN P A R T I A L F U L F I L M E N T O F T H E R E Q U I R E M E N T S F O R T H E D E G R E E OF D O C T O R OF P H I L O S O P H Y in T H E F A C U L T Y OF G R A D U A T E S T U D I E S (Department of Chemistry) We accept this thesis as conforming to the required standard T H E U N I V E R S I T Y OF B R I T I S H C O L U M B I A September, 2002 © Robert A . Britton, 2002 U B C Rare Books and Special Collections - Thesis Authorisation Form 06/09/02 15:59 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t of the requirements for an advanced degree at the U n i v e r s i t y of B r i t i s h Columbia , I agree that the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e for r e f e r e n c e and s tudy . I f u r t h e r agree that permis s ion for ex tens ive copying of t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the head of my department or by h i s or her r e p r e s e n t a t i v e s . I t i s understood that copying or p u b l i c a t i o n of t h i s t h e s i s f o r f i n a n c i a l ga in s h a l l not be a l lowed without my w r i t t e n p e r m i s s i o n . Department of The U n i v e r s i t y of B r i t i s h Columbia Vancouver, Canada Date http://www.library.ubc.ca/spcoll/thesauth. html Page I of 1 11 A b s t r a c t The ultimate goal in the chemotherapeutic treatment of cancer is the development of drugs that are highly effective against tumor cells and have little or no effect on healthy cells. K e y to this pursuit is the identification of differences that exist between the life cycle of normal and cancerous cells. Thus, the discovery of new small molecule inhibitors of enzyme…
has type: Thesis/Dissertation
date issued: 2002-11
is shown at: 10.14288/1.0061341
language: eng
degree discipline: Chemistry
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/13300