Goormaghtigh E, Huart P, Praet M, Brasseur R, Ruysschaert J M
Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles, Brussels, Belgium.
Biophys Chem. 1990 Apr;35(2-3):247-57. doi: 10.1016/0301-4622(90)80012-v.
Adriamycin and its derivatives are among the most efficient antimitotics used in clinical therapy. A specific cardiotoxicity places a limit on the total dose of adriamycin that may be administered. The mechanism of cardiac toxicity is complex. Data accumulated from in vitro and in vivo studies indicate a possible common cause for the inhibition of numerous enzymes and tissue degradation by a free radical mechanism: the binding of adriamycin to the inner mitochondrial membrane cardiolipin. The structure of the adriamycin-cardiolipin complex has been investigated by using physico-chemical techniques and via conformational analysis. The results open a rational way to design new structures that are less cardiotoxic.
阿霉素及其衍生物是临床治疗中使用的最有效的抗有丝分裂药物之一。特定的心脏毒性限制了可给药的阿霉素总剂量。心脏毒性的机制很复杂。体外和体内研究积累的数据表明，通过自由基机制抑制多种酶和组织降解可能存在一个共同原因：阿霉素与线粒体内膜心磷脂结合。已通过物理化学技术和构象分析研究了阿霉素 - 心磷脂复合物的结构。这些结果为设计心脏毒性较小的新结构开辟了一条合理的途径。
