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Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity.

par Goormaghtigh, Erik ;Huart, Pascal ;Praet, Michel;Brasseur, Robert ;Ruysschaert, Jean Marie
Référence Biophysical chemistry, 35, 2-3, page (247-257)
Publication Publié, 1990-04

Article révisé par les pairs

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Résumé :

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.