Dr Marc Devocelle and Prof Kevin Nolan
In cardiovascular diseases arteries can become blocked by thrombosis. Non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin are used as anti-thrombotic agents in preventing heart disease and stroke. Oxygen free radicals play a role in the induction of thrombosis and a greater understanding of the biochemical reactions of these free radicals could lead to the development of an improved therapeutic agent for treating and preventing cardiovascular diseases.
Professor Des Fitzgerald, Vice-President for Research at UCD, and Centre for Synthesis and Chemical Biology (CSCB) researchers Dr Marc Devocelle and Professor Kevin Nolan, from the Royal College of Surgeons in Ireland (RCSI), have recently synthesised some derivates of anthranilic hydroxamic acid (AHA). These AHA compounds have the potential to be developed as therapeutic agents for inhibiting the free radical activity that can contribute to cardiovascular diseases.
NSAIDs act by interfering with the release of prostaglandins. The biosynthetic process of producing prostaglandins starts with the biotransformation of arachidonic acid by an enzyme which is known to act at two sites - the cyclooxygenase (COX) site and the peroxidase (POX) site. Oxygen free radicals are generated at the POX site.
"Peroxidases are very powerful enzymes capable of generating highly damaging free radicals. The enzyme we are working on shows up in a number of major diseases, including atherosclerosis or hardening of the arteries," says Professor Fitzgerald. "Indeed, the first of our series of compounds slowed the development of atherosclerosis in the lab in a mouse model."
Publication reference:
Lee, J.; Chubb, A. J.; Moman, E.; McLoughlin, B. M.; Sharkey, C. T.; Kelly, J. G.; Nolan, K. B.; Devocelle, M.; Fitzgerald, D. J. Org. Biomol. Chem. 2005, 3, 3678-3685.
