TY - JOUR
T1 - 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
AU - Bensasson, René V.
AU - Zoete, Vincent
AU - Berthier, Gaston
AU - Talalay, Paul
AU - Dinkova-Kostova, Albena T.
N1 - Funding Information:
The authors are grateful for financial support from the American Cancer Society (Grant RSG-07-157-01-CNE ), the National Institutes of Health (Grants CA06793 and CA93780 ), Research Councils UK, Cancer Research UK (C20953/A10270), the Royal Society, the Anonymous Trust, Tenovus Scotland, the American Institute for Cancer Research, the Lewis B. and Dorothy Cullman Foundation, and W. Patrick McMullan and the McMullan Family Fund. The triterpenoids were kindly supplied by Drs. M.B. Sporn, T. Honda and G. Gribble, Dartmouth School of Medicine (Hanover, NH).
PY - 2010/7
Y1 - 2010/7
N2 - Electron affinity (EA) and electrophilicity index (ω) 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 ω 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.
AB - Electron affinity (EA) and electrophilicity index (ω) 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 ω 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.
KW - Electron affinity
KW - Inflammation
KW - NAD(P)H-quinone oxidoreductase 1
KW - Quantum chemical calculations
KW - Structure-activity relationships
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U2 - 10.1016/j.cbi.2010.04.026
DO - 10.1016/j.cbi.2010.04.026
M3 - Article
C2 - 20433811
AN - SCOPUS:77953539366
SN - 0009-2797
VL - 186
SP - 118
EP - 126
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
IS - 2
ER -