Potency ranking of triterpenoids as inducers of a cytoprotective enzyme and as inhibitors of a cellular inflammatory response via their electron affinity and their electrophilicity index

Rene V. Bensasson, Vincent Zoete, Gaston Berthier, Paul Talalay, Albena T. Dinkova-Kostova

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    Abstract

    Electron affinity (EA) and electrophilicity index (omega) of 16 synthetic triterpenoids (TP), previously identified as inducers of cytoprotective enzymes and as inhibitors of cellular inflammatory responses, have been calculated by the molecular orbital method. Linear correlations were obtained by plotting the values of EA, as well as those of omega versus (i) the potencies of induction of NAD(P)H quinone reductase (NQO1, EC 1.6.99.2), a cytoprotective enzyme, expressed via the concentration of TP required to double the specific activity of NQO1 (CD value) and (ii) the values of their anti-inflammatory activity expressed via the IC-50 of TP for suppression of upregulation of inducible nitric oxide synthase (iNOS, EC 1.14.13.39), both previously experimentally determined. The observed correlations demonstrate quantitatively for a series of triterpenoids that their electrophilicity is a major factor determining their potency as inducers of the cytoprotective phase 2 response and as inhibitors of inflammatory processes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)118-126
    Number of pages9
    JournalChemico-Biological Interactions
    Volume186
    Issue number2
    DOIs
    Publication statusPublished - 30 Jul 2010

    Keywords

    • Electron affinity
    • Inflammation
    • NAD(P)H-quinone oxidoreductase 1
    • Quantum chemical calculations
    • Structure-activity relationships
    • CDDO-METHYL ESTER
    • DENSITY-FUNCTIONAL THEORY
    • CANCER-PROTECTIVE ENZYME
    • NITRIC-OXIDE PRODUCTION
    • KOOPMANS THEOREM
    • PHASE-2 RESPONSE
    • ORBITAL ENERGIES
    • GENE-EXPRESSION
    • INDUCTION
    • CARCINOGENESIS

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