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

被引：15

作者：

Bensasson, Rene V. ^{[2
]}

Zoete, Vincent ^{[3
]}

Berthier, Gaston ^{[4
]}

Talalay, Paul ^{[5
]}

Dinkova-Kostova, Albena T. ^{[1
,5
]}

机构：

[1] Univ Dundee, Biomed Res Inst, Dundee DD1 9SY, Scotland

[2] Museum Natl Hist Nat, F-75231 Paris, France

[3] Swiss Inst Bioinformat, Mol Modeling Grp, Lausanne, Switzerland

[4] Univ Paris 06, Chim Theor Lab, Paris, France

[5] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2010年 / 186卷 / 02期

基金：

美国国家卫生研究院;

关键词：

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;

D O I：

10.1016/j.cbi.2010.04.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：118 / 126

页数：9

共 47 条

[11] Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action [J].