Discovery - University of Dundee - Online Publications

Library & Learning Centre

Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents

Standard

Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents. / Zheng, Suqing; Laxmi, Y. R. Santosh; David, Emilie; Dinkova-Kostova, Albena T.; Shiavoni, Katherine H.; Ren, Yanqing; Zheng, Ying; Trevino, Isaac; Bumeister, Ronald; Ojima, Iwao; Wigley, W. Christian; Bliska, James B.; Mierke, Dale F.; Honda, Tadashi.

In: Journal of Medicinal Chemistry, Vol. 55, No. 10, 24.05.2012, p. 4837-4846.

Research output: Contribution to journalArticle

Harvard

Zheng, S, Laxmi, YRS, David, E, Dinkova-Kostova, AT, Shiavoni, KH, Ren, Y, Zheng, Y, Trevino, I, Bumeister, R, Ojima, I, Wigley, WC, Bliska, JB, Mierke, DF & Honda, T 2012, 'Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents' Journal of Medicinal Chemistry, vol 55, no. 10, pp. 4837-4846.

APA

Zheng, S., Laxmi, Y. R. S., David, E., Dinkova-Kostova, A. T., Shiavoni, K. H., Ren, Y., Zheng, Y., Trevino, I., Bumeister, R., Ojima, I., Wigley, W. C., Bliska, J. B., Mierke, D. F., & Honda, T. (2012). Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents. Journal of Medicinal Chemistry, 55(10), 4837-4846doi: 10.1021/jm3003922

Vancouver

Zheng S, Laxmi YRS, David E, Dinkova-Kostova AT, Shiavoni KH, Ren Y et al. Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents. Journal of Medicinal Chemistry. 2012 May 24;55(10):4837-4846.

Author

Zheng, Suqing; Laxmi, Y. R. Santosh; David, Emilie; Dinkova-Kostova, Albena T.; Shiavoni, Katherine H.; Ren, Yanqing; Zheng, Ying; Trevino, Isaac; Bumeister, Ronald; Ojima, Iwao; Wigley, W. Christian; Bliska, James B.; Mierke, Dale F.; Honda, Tadashi / Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents.

In: Journal of Medicinal Chemistry, Vol. 55, No. 10, 24.05.2012, p. 4837-4846.

Research output: Contribution to journalArticle

Bibtex - Download

@article{e52a0d8d21d3458c8e35516365dd27a7,
title = "Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents",
author = "Suqing Zheng and Laxmi, {Y. R. Santosh} and Emilie David and Dinkova-Kostova, {Albena T.} and Shiavoni, {Katherine H.} and Yanqing Ren and Ying Zheng and Isaac Trevino and Ronald Bumeister and Iwao Ojima and Wigley, {W. Christian} and Bliska, {James B.} and Mierke, {Dale F.} and Tadashi Honda",
year = "2012",
volume = "55",
number = "10",
pages = "4837--4846",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents

A1 - Zheng,Suqing

A1 - Laxmi,Y. R. Santosh

A1 - David,Emilie

A1 - Dinkova-Kostova,Albena T.

A1 - Shiavoni,Katherine H.

A1 - Ren,Yanqing

A1 - Zheng,Ying

A1 - Trevino,Isaac

A1 - Bumeister,Ronald

A1 - Ojima,Iwao

A1 - Wigley,W. Christian

A1 - Bliska,James B.

A1 - Mierke,Dale F.

A1 - Honda,Tadashi

AU - Zheng,Suqing

AU - Laxmi,Y. R. Santosh

AU - David,Emilie

AU - Dinkova-Kostova,Albena T.

AU - Shiavoni,Katherine H.

AU - Ren,Yanqing

AU - Zheng,Ying

AU - Trevino,Isaac

AU - Bumeister,Ronald

AU - Ojima,Iwao

AU - Wigley,W. Christian

AU - Bliska,James B.

AU - Mierke,Dale F.

AU - Honda,Tadashi

PY - 2012/5/24

Y1 - 2012/5/24

N2 - Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.</p>

AB - Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-alpha and IL-1 beta with potencies that are higher than those of bardoxolone methyl and TBE-31.</p>

U2 - 10.1021/jm3003922

DO - 10.1021/jm3003922

M1 - Article

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 10

VL - 55

SP - 4837

EP - 4846

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy