Generation of Radical Anions of Nifurtimox and Related Nitrofuran Compounds By Ascorbate

Abstract

Nifurtimox analogues bearing triazol-4-yl, benzimidazol-1-yl, triazin-4-yl or related groups as counterpart of the (5-nitro-2-furfurylidene) amino group were reduced to their nitro anion radicals by ascorbate in anaerobic solutions at high pH. The ESR spectra of the radical anions showed hyperfine spin couplings restricted to the nitrofuran moiety. With these compounds, the spin density at the nitro group was greater than with nifurtimox, nitrofurazone and nitrofurantoin. At neutral pH, solutions containing ascorbate and nitrofuran derivatives consumed oxygen, the compounds bearing unsaturated nitrogen heterocycles being the most effective. Superoxide dismutase and catalase decreased the rate of oxygen consumption, thus demonstrating the production of superoxide and hydrogen peroxide, respectively. NMR spectra of the triazol-4-yl and triazin-4-yl nitrofuran derivatives showed a deshielding effect for the azomethine proton, which was undetectable with nifurtimox and nitrofurazone.

Key Words:

• Nitrofurans
• nitro anion radicals
• nifurtimox analogues
• ascorbate
• superoxide.