The long-term goals of this project are aimed at an understanding of the metabolic redox reactions which effect the effectiveness of purine anti-cancer drugs and at the development of instrumental methods as alternatives to animal experimentation in metabolic studies. Electrochemistry will be used in combination with mass spectrometry, separations, UV/vis, IR and NMR spectroscopy to determine electrochemical oxidation pathways of model purine antimetabolites. Mechanisms of initial electron transfer steps will be determined for those purine antimetabolites whose overall electrochemical oxidation pathways are the same as the pathways of enzymatic reactions catalyzed by enzymes of purine metabolism, xanthine oxidase and peroxidase. The compounds chosen for this study represent four classes of antimetabolites: thiopurines, aminopurines, chloropurines and deazapurine. All are known inhibitors of cell growth and their effectiveness is determined by metabolic reactions which involve oxidations and hydrolysis and whose pathways are largely unknown. New electrochemistry mass spectrometry and HPLC methods will be developed for identification of intermediates and products in the oxidation of purine drugs. The mechanistic information will be used to identify the conditions needed to simulate the enzymatic redox reactions electrochemically.
| Mackay, R A; Myers, S A; Bodalbhai, L et al. (1990) Microemulsion structure and its effect on electrochemical reactions. Anal Chem 62:1084-90 |
| Bodalbhai, L; Brajter-Toth, A (1988) Different methods of graphite electrode treatment and their effect on the electrochemical behavior of a small adsorbing biological molecule, 2,6-diamino-8-purinol. Anal Chem 60:2557-61 |
