NEW DRUGS TO ALLEVIATE ADRIAMYCIN CARDIOTOXICITY

拟议研究的长期目标是了解 氨基羧基稳定化合物独特的化学性质和生物学性质 自由基及其二聚体前体，利用这些自由基作为还原 测定蒽环类药物氧化还原化学性质的试剂 抗肿瘤药物，并开发这些自由基作为高血压病的救援剂 剂量阿霉素抢救疗法。具体目的是(1)比较 定量测定了不同的蒽环类化合物的化学反应活性 活性和/或毒性的潜在测量，(2)确定 蒽环类和TO中间态氧化还原态的反应性 建立蒽环类化合物作为指示剂的进一步催化作用 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用于 蒽环类药物和水溶性单自由基，两者都是潜在的救援手段 阿霉素类药物。 这项拟议研究的主要生物医学益处是新的。 对设计更好的抗肿瘤药物和化疗的认识 抗肿瘤药物控制的方案、新药和方法 无毒、无酶、生物的毒性及其发展 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.