NEW DRUGS TO ALLEVIATE ADRIAMYCIN CARDIOTOXICITY

拟议研究的长期目标是了解 独特的化学和生物性能的氨基羧基稳定 自由基及其二聚体前体，以利用这些自由基作为还原剂， 用于测定蒽环类抗生素氧化还原化学的试剂 抗肿瘤药物，并开发这些自由基作为救援剂的高 大剂量阿霉素补救治疗。 具体目的是：（1）比较 定量地研究了各种蒽环类药物作为 活性和/或毒性的潜在测量，（2）确定 蒽环类药物的中间氧化还原态的反应性， 进一步确定蒽环类药物的催化作用， 生物作用方式;（3）氨基羧基的合成与研究 稳定的双自由基作为多电子还原剂， 蒽环类和水溶性单自由基，两者都是潜在的救援 用于阿霉素的药剂。 拟议研究的主要生物医学效益是新的 设计更好的抗肿瘤药物和化疗的知识 用于控制抗肿瘤药物的方案、新药和方法 开发无毒、无酶、生物 还原剂

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.