NEW DRUGS TO PREVENT REPERFUSION ISCHEMIA INJURY

THIS RESEARCH IS BASED ON THE THESIS THAT OXYGEN-FREE RADICALS CONTRIBUTE IN A SIGNIFICANT WAY TO THE DELETERIOUS ASPECT OF REPERFUSION AFTER A TISSUE OR ORGAN IS DEPRIVED OFOXYGEN AND FLOW IS RE-INITIATED. THE OBJECTIVE OF THIS RESEARCH IS TO DETERMINE THE POTENTIAL OF A NEW SERIES OF COMPOUNDS TO PROTECT AGAINST ISCHEMIA REPERFUSION INJURY. THESE COMPOUNDS, ORIGINALLY DEVELOPED FOR CANCER CHEMOTHERAPY, HAVE FREE RADICAL SCAVENGING AND ANTI-INFLAMMATORY ACTIVITY. REPRESENTATIVE FUNCTIONAL GROUPS WILL BE INSERTED, AND IN VITRO EXPERIMENTS WILL BE PERFORMED TO EVALUATE THE ABILITY OF EACH SUBCLASS TO SCAVENGE FREE RADICALS, INCLUDING THE SUPEROXIDE AND HYDROXYL RADICALS. THE FE-CHELATING CAPACITY OF THE DIFFERENT CONGENERS, AN ATTRIBUTE OF THESE COMPOUNDS, WILL BE MEASURED TO EVALUATE WHICH PART OF THE STRUCTURE CONTRIBUTES TO BIOLOGICAL ACTIVITY FOR NEW DRUG DESIGN. FINALLY, THE EFFICACY OF THE COMPOUNDS TO PREVENT REPERFUSION ISCHEMIA INJURY WILL BE PERFORMED IN THE PERFUSED RABBIT HEART MODEL. THE DRUG EFFECT ON THE FORMATION OF OXYGEN-FREE RADICALS ON REPERFUSION AS DETERMINED BY EPR TECHNIQUES WILL BE MEASURED. SIMULTANEOUSLY WITH THE EPR FREE RADICAL MEASUREMENTS IN THE PERFUSED HEARTS, THE FUNCTIONAL CAPACITYOF THE HEART WILL ALSO BE MEASURED. THE GENERATION OF FREE RADICALS FROM THE DRUG MOLECULE IS EXPECTED, AND IT IS PLANNED TO MONITOR FOR SUCH RADICALS.