| Summary: | The electrochemical properties of 24 1,4-dioxidoquinoxalin-2-yl ketone derivatives with varying
degrees of anti-Chagas activity were investigated in the aprotic solvent dimethylformamide (DMF) by
cyclic voltammetry and first-derivative cyclic voltammetry. For this group of compounds, the first
reduction in DMF was either reversible or quasireversible and consistent with reduction of the N-oxide
functionality to form the radical anion. The second reduction process for these compounds was
irreversible under the conditions used. The reduction potentials correlated well with molecular structure.
Substitution in the 3-, 6-, and 7- positions of the quinoxaline ring by electron-withdrawing substituents
directly affected the ease of reduction and improved the biological activities of these compounds,
whereas substitution by electron-donating groups had the opposite effect. The electrochemical results,
when combined with previous work on their mechanism of action against Chagas disease and their
measured anti-Chagas activities, indicated that the quinoxaline 1,4-dioxide system serves as a promising
starting point for chemical modifications aimed at improving the T. cruzi activity via a possible
bioreduction mechanism.
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