Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes

Research output: Contribution to journalArticle

201 Citations (Scopus)

Abstract

A series of naturally occurring as well as synthetic structural analogs of the dietary constituent curcumin were examined in order to elucidate which portions of the molecule are critical for the ability to induce Phase 2 detoxification enzymes in murine hepatoma cells, and hence to assess the chemoprotective potential of these compounds. Two groups of compounds were studied: classical Michael reaction acceptors such as curcumin and related β-diketones such as dibenzoylmethane which lack direct Michael reactivity. The presence of two structural elements was found to be required for high inducer potency: (i) hydroxyl groups at ortho-position on the aromatic rings and (ii) the β-diketone functionality. All curcuminoids elevate the specific activity of quinone reductase in both wild type and mutant cells defective in either the aryl hydrocarbon (Ah) receptor or cytochrome P4501A1 activity. This indicates that neither binding to this receptor, nor metabolic activation by P4501A1 are required for the signaling process originating from this family of electrophiles and ultimately resulting in Phase 2 enzyme induction.

Original languageEnglish
Pages (from-to)911-914
Number of pages4
JournalCarcinogenesis
Volume20
Issue number5
DOIs
Publication statusPublished - 1 May 1999

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Curcumin
NAD(P)H Dehydrogenase (Quinone)
Aryl Hydrocarbon Receptors
Enzyme Induction
Enzymes
Cytochromes
Hydroxyl Radical
Hepatocellular Carcinoma
dibenzoylmethane
Metabolic Activation

Cite this

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abstract = "A series of naturally occurring as well as synthetic structural analogs of the dietary constituent curcumin were examined in order to elucidate which portions of the molecule are critical for the ability to induce Phase 2 detoxification enzymes in murine hepatoma cells, and hence to assess the chemoprotective potential of these compounds. Two groups of compounds were studied: classical Michael reaction acceptors such as curcumin and related β-diketones such as dibenzoylmethane which lack direct Michael reactivity. The presence of two structural elements was found to be required for high inducer potency: (i) hydroxyl groups at ortho-position on the aromatic rings and (ii) the β-diketone functionality. All curcuminoids elevate the specific activity of quinone reductase in both wild type and mutant cells defective in either the aryl hydrocarbon (Ah) receptor or cytochrome P4501A1 activity. This indicates that neither binding to this receptor, nor metabolic activation by P4501A1 are required for the signaling process originating from this family of electrophiles and ultimately resulting in Phase 2 enzyme induction.",
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Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes. / Dinkova-Kostova, Albena T.; Talalay, Paul.

In: Carcinogenesis, Vol. 20, No. 5, 01.05.1999, p. 911-914.

Research output: Contribution to journalArticle

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