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Title: Chemical, biological and molecular approaches toward drug discovery from marine organisms
Author: Houssen, Wael E.
ISNI:       0000 0001 3582 3689
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2006
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The first chapter provides a comprehensive review on the current status of drug discovery from the sea, the hurdles encountered and the future trends.  The second chapter describes the use of biologically guided fractionation to isolate cytotoxic compounds from the marine ascidian Sigillina signifera.  The main outcome was the isolation and identification of four known compounds identified as 4-methoxy-2,2’-bipyrrole-5-carboxaldehyde, tambjamine C, tambjamine F and phenyl ethylamine.  The first three compounds were shown to be responsible for the cytotoxicity shown by the crude extract.  The third chapter describes the isolation and identification of a new 4-hydroxybenzoyl derivative from the aqueous extract of the marine hydroid Campanularia sp. using NMR-guided fractionation.  In spite of its structural resemblance to some potent histone deacetylase inhibitors, the new compound has proved to completely lack such activity.  The fourth and fifth chapters describe the use of electrophysiological techniques and Ca2+ imaging to investigate the effects of two compounds on the behaviour of different ion channels expressed on cultured DRG neurones.  The first compound, latrunculin A, was shown to alter channels behaviour through disruption of the actin cytoskeleton.  This study offers a new biological screen for compounds that act through the same mechanism of action.  The second compound, trigonelline, was shown to induce neuronal excitability in cultured DRG neurones by suppressing the outward voltage-activated potassium current.  The last chapter describes the cloning of patE gene as part of the efforts toward cloning of the gene cluster encoding the biosynthesis of the cyclic octapeptides patellamides, ascidiacyclamide and ulithiacyclamides from Prochloron didemni, the cyanobacterial symbiont of the tropical ascidian Lissoclinum patella.  The aim of the project is to get a sustainable supply of such biologically active compounds.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available