Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent

Tadashi Honda; Albena T. Dinkova-Kostova; Emilie David; Eric M. Padegimas; Chitra Sundararajan; Melean Visnick; Ron Bumeister; W. Christian Wigley

doi:10.1016/j.bmcl.2011.03.018

Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent

Tadashi Honda, Albena T. Dinkova-Kostova, Emilie David, Eric M. Padegimas, Chitra Sundararajan, Melean Visnick, Ron Bumeister, W. Christian Wigley

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

To explore more potent N-acylimidazole analogues of CDDO than CDDO-Im, which is one of the most potent compounds in several widely used bioassays related to protection against inflammation and carcinogenesis; we have synthesized and evaluated five new N-acyl(acetylenic) imidazole analogues. Among them, 4-ethynylimidazole 4 is nearly equivalent to CDDO-Im in potency in these bioassays. Remarkably, the solid form of 4 is more stable than that of CDDO-Im. These findings suggest that 4 is a very promising anti-inflammatory and cytoprotective agent and its further preclinical evaluation is warranted. (C) 2011 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	2188-2191
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2011.03.018
Publication status	Published - 15 Apr 2011

Keywords

Triterpene
Oleanolic acid
Acetylenicimidazole
Inhibitors of nitric oxide production
Inducers of heme oxygenase-1
NQO1
NITRIC-OXIDE PRODUCTION
URSANE TRITERPENOIDS
MOUSE MACROPHAGES
PROTECTION
INHIBITORS
AFLATOXIN
PATHWAYS
OLEANANE
RING

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10.1016/j.bmcl.2011.03.018

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Honda, T., Dinkova-Kostova, A. T., David, E., Padegimas, E. M., Sundararajan, C., Visnick, M., Bumeister, R., & Wigley, W. C. (2011). Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent. Bioorganic & Medicinal Chemistry Letters, 21(8), 2188-2191. https://doi.org/10.1016/j.bmcl.2011.03.018

Honda, Tadashi ; Dinkova-Kostova, Albena T. ; David, Emilie ; Padegimas, Eric M. ; Sundararajan, Chitra ; Visnick, Melean ; Bumeister, Ron ; Wigley, W. Christian. / Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent. In: Bioorganic & Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 8. pp. 2188-2191.

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title = "Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent",

abstract = "To explore more potent N-acylimidazole analogues of CDDO than CDDO-Im, which is one of the most potent compounds in several widely used bioassays related to protection against inflammation and carcinogenesis; we have synthesized and evaluated five new N-acyl(acetylenic) imidazole analogues. Among them, 4-ethynylimidazole 4 is nearly equivalent to CDDO-Im in potency in these bioassays. Remarkably, the solid form of 4 is more stable than that of CDDO-Im. These findings suggest that 4 is a very promising anti-inflammatory and cytoprotective agent and its further preclinical evaluation is warranted. (C) 2011 Elsevier Ltd. All rights reserved.",

keywords = "Triterpene, Oleanolic acid, Acetylenicimidazole, Inhibitors of nitric oxide production, Inducers of heme oxygenase-1, NQO1, NITRIC-OXIDE PRODUCTION, URSANE TRITERPENOIDS, MOUSE MACROPHAGES, PROTECTION, INHIBITORS, AFLATOXIN, PATHWAYS, OLEANANE, RING",

author = "Tadashi Honda and Dinkova-Kostova, {Albena T.} and Emilie David and Padegimas, {Eric M.} and Chitra Sundararajan and Melean Visnick and Ron Bumeister and Wigley, {W. Christian}",

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doi = "10.1016/j.bmcl.2011.03.018",

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Honda, T, Dinkova-Kostova, AT, David, E, Padegimas, EM, Sundararajan, C, Visnick, M, Bumeister, R & Wigley, WC 2011, 'Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent', Bioorganic & Medicinal Chemistry Letters, vol. 21, no. 8, pp. 2188-2191. https://doi.org/10.1016/j.bmcl.2011.03.018

Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent. / Honda, Tadashi; Dinkova-Kostova, Albena T.; David, Emilie; Padegimas, Eric M.; Sundararajan, Chitra; Visnick, Melean; Bumeister, Ron; Wigley, W. Christian.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 21, No. 8, 15.04.2011, p. 2188-2191.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent

AU - Honda, Tadashi

AU - Dinkova-Kostova, Albena T.

AU - David, Emilie

AU - Padegimas, Eric M.

AU - Sundararajan, Chitra

AU - Visnick, Melean

AU - Bumeister, Ron

AU - Wigley, W. Christian

PY - 2011/4/15

Y1 - 2011/4/15

N2 - To explore more potent N-acylimidazole analogues of CDDO than CDDO-Im, which is one of the most potent compounds in several widely used bioassays related to protection against inflammation and carcinogenesis; we have synthesized and evaluated five new N-acyl(acetylenic) imidazole analogues. Among them, 4-ethynylimidazole 4 is nearly equivalent to CDDO-Im in potency in these bioassays. Remarkably, the solid form of 4 is more stable than that of CDDO-Im. These findings suggest that 4 is a very promising anti-inflammatory and cytoprotective agent and its further preclinical evaluation is warranted. (C) 2011 Elsevier Ltd. All rights reserved.

AB - To explore more potent N-acylimidazole analogues of CDDO than CDDO-Im, which is one of the most potent compounds in several widely used bioassays related to protection against inflammation and carcinogenesis; we have synthesized and evaluated five new N-acyl(acetylenic) imidazole analogues. Among them, 4-ethynylimidazole 4 is nearly equivalent to CDDO-Im in potency in these bioassays. Remarkably, the solid form of 4 is more stable than that of CDDO-Im. These findings suggest that 4 is a very promising anti-inflammatory and cytoprotective agent and its further preclinical evaluation is warranted. (C) 2011 Elsevier Ltd. All rights reserved.

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KW - Oleanolic acid

KW - Acetylenicimidazole

KW - Inhibitors of nitric oxide production

KW - Inducers of heme oxygenase-1

KW - NQO1

KW - NITRIC-OXIDE PRODUCTION

KW - URSANE TRITERPENOIDS

KW - MOUSE MACROPHAGES

KW - PROTECTION

KW - INHIBITORS

KW - AFLATOXIN

KW - PATHWAYS

KW - OLEANANE

KW - RING

U2 - 10.1016/j.bmcl.2011.03.018

DO - 10.1016/j.bmcl.2011.03.018

M3 - Article

C2 - 21441026

VL - 21

SP - 2188

EP - 2191

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 8

ER -

Honda T, Dinkova-Kostova AT, David E, Padegimas EM, Sundararajan C, Visnick M et al. Synthesis and biological evaluation of 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4-ethynylimidazole. A novel and highly potent anti-inflammatory and cytoprotective agent. Bioorganic & Medicinal Chemistry Letters. 2011 Apr 15;21(8):2188-2191. https://doi.org/10.1016/j.bmcl.2011.03.018