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Redox Parameters Associated to Cytotoxic and Antitumor Activities in the Series of Antitumor Drugs Ellipticines and Derivatives

  • Christian Auclair
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 264)

Abstract

Generation of virtual DNA breaks through the alteration of the catalytic activity of topoisomerase II are displayed by the most successful antitumor drugs in clinical use including adriamycin, m-AMSA, hydroxy ellipticine derivatives, raitoxantrone and VP-16 (Nelson et al., 1984; Tewey et al., 1984; Rowe et al., 1986). This feature is thought to be responsible for the selective cytotoxic effect leading to the antitumor activity of these drugs, comparative studies of the physicochemical properties of antitumor topoisomerase inhibitors clearly show that the single parameter that they share in common is the capability to be oxidized to reactive metabolites through one-electron transfer process (Auclair, 1987). Along this line, most of them are able to undergo autoxidation generating oxy-radicals (Dorowshow, 1983; Auclair et al., 1983a; Auclair, 1987; Nakasawa et al., 1985; Kovacic et al., 1986) and are substrate for peroxidases (Auclair & Paoletti, 1981; Auclair et al., 1986; Auclair, 1987; Trush, 1982; Shina et al., 1983, 1984; Reszha et al., 1986; Haim et al., 1987). In view of rational design and screening of new antitumor topoisomerase modifiers, we have attempted to characterize significant parameter(s) in terms of redox properties associated to cytotoxic activity on malignant cells. This study has been made possible in the series of ellipticine in which are available, number of derivatives displaying various cytotoxic activity associated to limited structural modifications.

Keywords

Methyl Linoleate Phenolic Group Antitumor Drug Bond Dissociation Energy Cleavable Complex 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Christian Auclair
    • 1
  1. 1.Laboratoire de Biochimie-Enzymologie, INSERM U 140, CNRS UA 147Institut Gustave RoussyVillejuif CedexFrance

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