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  • Title: Ellipticine, 9-hydroxyellipticine, and 9-hydroxyellipiticinum: some biochemical properties of possible pharmacologic significance.
    Author: Paoletti C, Auclair C, Lesca P, Tocanne JF, Malvy C, Pinto M.
    Journal: Cancer Treat Rep; 1981; 65 Suppl 3():107-18. PubMed ID: 7049365.
    Abstract:
    Ellipticine, 5,11-dimethyl-(6H)-pyrido-(4,3,b)-carbazole (NSC 71795) is a potent cytotoxic and antitumor agent. Several of its derivatives share these properties and nine hydroxylated compounds are even more potent. 2-Methyl-9-hydorxyellipticinium (NSC 264-137) has thus recently been shown to display some therapeutic effectiveness in human breast cancers. The biochemical mechanism of this action is discussed in this paper. DNA has been implied as the target of ellipticine and some derivatives; however, these drugs do not break DNA in cultured L1210 cells. Moreover, several other biochemical constituents are able to bind these compounds in vitro as efficiently as DNA. In this paper the interactions between ellipticine and some of those derivatives and (a) ascitic phospholipids monolayers and (b) cytochrome P450 microsomal proteins are studied and discussed. Finally, the hypothesis that the nonhydroxylated ellipticine derivatives might be better cytotoxic agents because they can be oxidized and generate free radical species through a monovalent electron transfer process is presented. This hypothesis is supported by experiments carried out on the oxidation of 9-hydroxyellipticine and 2-methyl-9-hydroxyellipticine by peroxidases.
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