RT Journal Article
SR Electronic
T1 The biooxidation of cytotoxic ellipticine derivatives: a key to structure-activity relationship studies?
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 93
OP 102
VO 33
IS 1
A1 G Meunier
A1 D De Montauzon
A1 J Bernadou
A1 G Grassy
A1 M Bonnafous
A1 S Cros
A1 B Meunier
YR 1988
UL http://molpharm.aspetjournals.org/content/33/1/93.abstract
AB In the family of ellipticine derivatives, those with an amino-phenol or a masked amino-phenol structure are among the most cytotoxic compounds. Preliminary studies on 9-hydroxy- or 9-methoxyellipticines have shown that these molecules behave as "pro-alkylating" agents. In order to rationalize the "biooxidative alkylation" process for various ellipticine derivatives, we report in the present article (i) their electrochemical oxidation parameters, (ii) their biochemical oxidation, (iii) the ability of the oxidized forms to form adducts with nucleophiles, (iv) the biological activities, and (v) the electronic properties of oxidized forms. We present some possible correlations between the oxidizability, the electrophilicity of the oxidized derivatives, and the biological activities of the corresponding drugs.