Scavenging activity of C4-hydroxyphenyl- and polyhydroxyphenyl-1,4-dihydropyridines toward free radicals

Authors

  • Ricardo Salazar,

    1. Laboratorio de Electrocatálisis, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile
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  • V. Pardo-Jimenez,

    1. Laboratorio de Bioelectroquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
    2. Laboratorio de Síntesis Orgánica y Modelación Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • P. A. Navarrete-Encina,

    1. Laboratorio de Síntesis Orgánica y Modelación Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • J. A. Squella,

    1. Laboratorio de Bioelectroquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • C. Camargo,

    1. Laboratorio de Antidopaje y Drogas de Abuso, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
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  • Luis J. Núñez-Vergara

    Corresponding author
    1. Laboratorio de Bioelectroquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
    • Laboratorio de Bioelectroquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile
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Abstract

The radical-scavenging ability of synthesized C4-phenolic-substituted 1,4-dihydropyridines (1,4-DHPs) toward 2,2-diphenyl-1-picrylhydrazyl (DPPH) and alkyl/alkylperoxyl ABAP-derived radicals at pH 7.4 was assessed by UV–visible spectroscopy. Reactivity of 1,4-DHPs toward DPPH was measured by following the decay of the absorption corresponding to the radical λmax at 525 nm, permitting the calculation of EC50, tEC50, and antiradical efficiency values. Pseudo–first-order kinetic rate constants for the reactivity between the C4-phenolic-substituted 1,4-DHP compounds and alkyl/alkylperoxyl ABAP-derived radicals were followed by the decrease in λmax at 356 nm corresponding to 1,4-DHP moiety. C4-phenolic-substituted 1,4-DHPs were more reactive toward alkyl free radicals than the other tested radicals. The 3,4,5-trihydroxyphenyl-1,4-DHP was the most reactive derivative toward this radical with a kinetic rate constant value of 513.2 s−1. Also, this derivative was the most effective toward the DPPH radical with the lowest EC50 value (5.08 µM). Comparative studies revealed that synthesized 1,4-DHPs were more reactive than commercial 1,4-DHPs. The scavenging mechanism involves the contribution of both pharmacophores, that is, hydroxyphenyl and 1,4-DHP rings, which was supported by the identification of the reaction products. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 810–820, 2012

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