Reactivity of the one-electron reduction product from nifedipine with relevant biological targets

• Published in: Chemico-biological interactions Vol. 101; no. 2; pp. 89 - 101
• Main Authors: Núñez-Vergara, Luis J., Navarrete-Encina, P.A., Ortiz, M.E., Bollo, S., Squella, J.A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 14.08.1996
• Subjects: Calcium Channel Blockers - chemistry; Cyclic voltammetry; Endobiotics; Glutathione - chemistry; Hydrogen-Ion Concentration; Nifedipine; Nifedipine - chemistry; Oxidation-Reduction; Xenobiotics; Xenobiotics - chemistry; Cyclic voltammetry; Endobiotics; Xenobiotics; Nifedipine
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/0009-2797(96)03714-3

The reactivity of the electrochemically generated nitro radical anion from nifedipine, a nitro aryl 1,4-dihydropyridine derivative, with relevant endobiotics and thiol-containing xenobiotics, was quantitatively assessed by cyclic voltammetry. The method was based on the decrease in the return-to-forward peak current ratio after the addition of compounds. A quantitative procedure to calculate the respective interaction constants between the radicals and the xeno/endobiotics is also provided. In the optimal selected conditions, i.e. mixed media (0.015 M aqueous citrate/DMF: 40/60, 0.3 M KCl, 0.1 TBAI) at pH 9.0 the following order of reactivity was obtained: glutathione > uracil > adenine and cysteamine > N-acetylcysteine > captopril > penicillamine. In all cases, the interaction rate constants for these derivatives were greater than the natural decay constant of the radical. Studies on the reactivity at pH 7.4 were also conducted. Results from these experiments indicate a significant reactivity between the radical and the endo/xenobiotics. The increase in the stability of the radical anion by increasing the pH of the mixed media resulted in a decreased reaction with the endo/xenobiotics tested. Computerized simulation with DIGISIM 2.0 of the proposed mechanisms fitted very well with the experimental results for both the natural decay of the radical and its reaction with the tested compounds.