NEW DRUGS TO ALLEVIATE ADRIAMYCIN CARDIOTOXICITY

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The long-term objectives of the proposed research are to understand the unique chemical and biological properties of amino carboxy stabilized radicals and their dimer precursors, to utilize these radicals as reducing agents for determination of the redox chemistry of the anthracycline anti-tumor drugs, and to develop these radicals as rescue agents for high dose adriamycin rescue therapy. The specific aims are (1) to compare quantitatively the chemical reactivity of various anthracyclines as a potential measure of activity and/or toxicity, (2) to determine the reactivity of intermediate redox states of the anthracyclines and to establish further catalytic roles for the anthracyclines as indicators of biological modes of action, (3) to synthesize and study amino carboxy stabilized diradicals as multiple electron reducing agents for the anthracyclines and water soluble mono-radicals, both as potential rescue agents for adriamycin. The primary biomedical benefits from the proposed research are new knowledge for the design of better anti-tumor drugs and chemotherapy protocols, new drugs and methods for the control of anti-tumor drug toxicity and the development of non-toxic, non-enzymatic, biological reducing agents.