[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Goormaghtigh, E; Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles, Brussels, Belgium
Huart, P; Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles - CP 206/2, B-1050 Brussels, Belgium
Praet, M; Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles - CP 206/2, B-1050 Brussels, Belgium
Brasseur, Robert ; Université de Liège - ULiège > Département GxABT > Chemistry for Sustainable Food and Environmental Systems (CSFES) ; Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles - CP 206/2, B-1050 Brussels, Belgium
Ruysschaert, J M; Laboratoire de Chimie-Physique des Macromolécules aux Interfaces, Université Libre de Bruxelles - CP 206/2, B-1050 Brussels, Belgium
Language :
English
Title :
Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity.
E.G. is an Action de Recherche ConcertCe (A.R.C., Belgium) Fellow. P.H. is an IRSIA Fellow and R.B. is a Research Associate of the National Fund for Scientific Research (Belgium). We are grateful to the Banque Nationale de Belgique and the Caisse GCntrale d’Epargne et de Retraite - Fonds Canctrologique for financial support. We are indebted to P. Duquenoy for expert technical assistance.
Lorenzina-Fiallo, Garnier-Suillerot (1986) Interaction of adriamycin with cardiolipin-containing vesicles. Evidence of an embedded site for the dihydroanthraquinone moiety. Biochimica et Biophysica Acta (BBA) - Biomembranes 854:142.
