Redox chemistry of the 9-anilinoacridine class of antitumor agents.
9-Anilinoacridines bearing a 1'-NHR substituent on the anilino ring undergo facile, chemically reversible, two-electron oxidation to quinone diimines. The chemical and electrochemical oxidation of three groups of 9-anilinoacridines (1'-substituted derivatives, together with 3'-substituted analogues and acridine-substituted analogues of the clinical antileukemic drug amsacrine) have been studied and their redox potentials determined. For aniline-substituted derivatives, redox potentials (E1/2) correlate well with substituent electronic properties, with electron-donating substituents facilitating oxidation. Substituents in the acridine ring have little effect on redox potentials, indicating minimal transmission of electronic effects from the acridine to the aniline rings. Although the broad class of 9-anilinoacridines show biological activity over a very wide range of structural variations, a 1'-NHR substituent is a common feature of the most active derivatives. Nevertheless, no clear quantitative relationships between redox potential and biological activity could be discerned, and the relevance of this redox chemistry to the mode of action of amsacrine and other 9-anilinoacridines remains unclear.
D000609:Aminoacridines / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000970:Antineoplastic Agents; D004247:DNA / Q000378:metabolism; D004563:Electrochemistry; D010084:Oxidation-Reduction; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D000609:Aminoacridines; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004247:DNA