Adenosine and adenosine analogues are recognised as cardioprotective agents due to the responses that they induce through the activation of myocardial adenosine receptors. Antioxidants such as nitroxide radicals have also been found to possess cardioprotective properties in biological systems, namely through their ability to scavenge the oxygen-based free radicals that are potentially damaging to tissues and cells. It was envisaged that the linking of an antioxidant moiety to adenosine would produce an adenosine analogue that activates adenosine receptors and also scavenges oxygen-derived free radicals in the body. Consequently, one aim of this project was to synthesise a series of adenosine analogues that possessed a nitroxide or a phenolic antioxidant at the N6 position of the adenosine skeleton.
Allosteric ligands have several advantages over orthosteric ligands as potential therapeutic agents, and research into the allosteric enhancement of adenosine receptors is a burgeoning field. It was envisaged that the linking of an antioxidant moiety to an allosteric enhancer would produce a compound that enhances the response of endogenous activation of adenosine receptors and also scavenges oxygen-based free radicals in the body. Consequently, a second aim of this project was to synthesise a series of allosteric enhancers of the A1 adenosine receptor that possessed antioxidant capability endowed by a nitroxide or a phenolic antioxidant functionality.
This project has resulted in the synthesis and characterisation of 19 novel N6 substituted adenosine analogues, and additionally 12 novel derivatised thiophenes. Each of the target compounds was tested for its ability to bind to each of the adenosine receptor subtypes and some analogues were found to be potent and selective adenosine receptor agonists.
| Identifer | oai:union.ndltd.org:ADTP/265621 |
| Date | January 2006 |
| Creators | Gregg, Alison Dianne |
| Publisher | Queensland University of Technology |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
| Rights | Copyright Alison Dianne Gregg |
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