Thiol-mediated processes play a key role to induce or inhibit inflammation proteins. Tailoring the reactivity of electrophiles can enhance the selectivity to address only certain surface cysteines. Fourteen 2,3,4,4-tetramethoxychalcones with different -X substituents (X=H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) were synthesized, containing the potentially electrophilic ,-unsaturated carbonyl unit. The assessment of their reactivity as electrophiles in thia-Michael additions with cysteamine shows a change in the reactivity of more than six orders of magnitude. Moreover, a clear correlation between their reactivity and an influence on the inflammation proteins heme oxygenase-1 (HO-1) and the inducible NO synthase (iNOS) is demonstrated. As the biologically most active compound, the -CF3-chalcone is shown to inhibit the NO production in RAW264.7 mouse macrophages in the nanomolar range.
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, England
Univ Salford, Ctr Mol Drug Design, Salford M5 4WT, Lancs, England
Clermont Univ, ENSCCF, EA987, Lab Chim Heterocyles & Glucides, F-63174 Aubiere, FranceUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Ducki, Sylvie
Rennison, David
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Rennison, David
Woo, Meiko
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Woo, Meiko
Kendall, Alexander
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Kendall, Alexander
Chabert, Jeremie Fournier Dit
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Univ Salford, Ctr Mol Drug Design, Salford M5 4WT, Lancs, England
Clermont Univ, ENSCCF, EA987, Lab Chim Heterocyles & Glucides, F-63174 Aubiere, FranceUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Chabert, Jeremie Fournier Dit
McGown, Alan T.
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Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, England
Univ Salford, Ctr Mol Drug Design, Salford M5 4WT, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
McGown, Alan T.
Lawrence, Nicholas J.
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Univ S Florida, Dept Interdisciplinary Oncol, H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USAUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
机构:
Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, England
Univ Salford, Ctr Mol Drug Design, Salford M5 4WT, Lancs, England
Clermont Univ, ENSCCF, EA987, Lab Chim Heterocyles & Glucides, F-63174 Aubiere, FranceUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Ducki, Sylvie
Rennison, David
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Rennison, David
Woo, Meiko
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h-index: 0
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Woo, Meiko
Kendall, Alexander
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h-index: 0
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Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Kendall, Alexander
Chabert, Jeremie Fournier Dit
论文数: 0引用数: 0
h-index: 0
机构:
Univ Salford, Ctr Mol Drug Design, Salford M5 4WT, Lancs, England
Clermont Univ, ENSCCF, EA987, Lab Chim Heterocyles & Glucides, F-63174 Aubiere, FranceUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Chabert, Jeremie Fournier Dit
McGown, Alan T.
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h-index: 0
机构:
Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC Drug Dev Grp, Manchester M20 4BX, Lancs, England
Univ Salford, Ctr Mol Drug Design, Salford M5 4WT, Lancs, EnglandUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
McGown, Alan T.
Lawrence, Nicholas J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Manchester, Dept Chem, Manchester M60 1QD, Lancs, England
Univ S Florida, Dept Interdisciplinary Oncol, H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USAUniv Manchester, Dept Chem, Manchester M60 1QD, Lancs, England