BIOCHEMICAL PHARMACOLOGY OF NEW ANTHRACYCLINES

这项研究的总体目标是建立基础生物化学 关于抗肿瘤蒽环类药物作用方式的信息， 生化事件的结构-活性关系， 是毒性和/或细胞毒性的原因（自由基生成，脂质 过氧化和DNA损伤），以及对代谢的影响， 使用体外灌注的大鼠肝脏清除选定的蒽环类抗生素， 完整的老鼠 我们希望这些基本信息将（1）有助于 行动方式概念的发展和评价 其中初始生物活化最终导致抗肿瘤的蒽环类 行动，（2）提供知识的代谢和处置的选择 在啮齿类动物中表现出高抗肿瘤和/或低毒性的化合物 测试系统，和（3）促进新的抗肿瘤药物的合理开发 蒽环类

The overall goal for this research is to establish basic biochemical information on the mode of action of antitumor anthracyclines, on the structure-activity relationships for the biochemical events considered to be the cause(s) of toxicity and/or cytotoxicity (radical generation, lipid peroxidation, and DNA damage), and on the metabolic disposition and clearance of selected anthracyclines using perfused rat livers in vitro and the intact rat. We expect that this basic information will (1) contribute to the development and evaluation of concepts on the mode of action of the anthracyclines wherein initial bioactivation leads ultimately to antitumor action, (2) provide knowledge of the metabolism and disposition of selected compounds that exhibit high antitumor and/or lower toxicities in rodent test systems, and (3) stimulate the rational development of new antitumor anthracyclines.