NEW TARGET-DIRECTED PT-PORPHYRIN ANTICANCER DRUGS

THE OBJECTIVE OF THIS PROJECT IS TO IMPROVE THE SELECTIVITY OF ACTION OF PLATINUM ANTITUMOR AGENTS. PLATINUM COMPOUNDS HAVE SHOWN ACTIVITY IN MANY TYPES OF TUMORS, BUT SEVERE DOSE-LIMITING SIDE EFFECTS HAVE AFFECTED THEIR CLINICAL UTILITY. BY DIRECTING THESE AGENTS MORE SPECIFICALLY TO TUMOR SITES, THEIR EFFECTIVENESS SHOULD BE IMPROVED. THE APPROACH USED TO ACHIEVE THIS IMPROVED SPECIFICITY WILL BE TO LINK THEM TO SYNTHETIC PORPHYRINS THAT ARE KNOWN TO HAVE TUMORLOCALIZING PROPERTIES. PLATINUM COMPLEXES HAVING KNOWN ANTITUMOR ACTIVITY WILL BE CHEMICALLY REACTED WITH SUBSTITUTED TETRAPHENYLPORPHYRIN COMPOUNDS. THE REACTION CONDITIONS WILL ASSURE STABLE BINDING OF THE ACTIVE PT MOIETY TO THE SUBSTITUENT SITES ON THE PORPHYRIN RING RATHER THAN AT THE CENTRAL SITE. IN THISWAY, THE PORPHYRIN THAT ACCUMULATES IN TUMOR TISSUE CAN ACT AS A CARRIER TO THE TUMOR FOR THE ACTIVE PT SPECIES. THE SUCCESS OF THIS PROGRAM WILL LEAD TO NEW, MORE SPECIFIC ANTITUMOR AGENTS, A MAJOR GOAL IN THE DESIGN OF NEW DRUGS.