Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity.
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.
Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles, Brussels, Belgium.
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E
Goormaghtigh
P
P
Huart
M
M
Praet
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R
Brasseur
J M
JM
Ruysschaert
D000818:Animals; D002308:Cardiolipins / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004317:Doxorubicin / Q000378:metabolism / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism
D002308:Cardiolipins; D004317:Doxorubicin