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<p>Previously unknown chalcones such as <i>β</i>’-chalcanone-<i>α</i>,<i>β</i>-diols and a <i>β</i>-hydroxydihydrochalcone, named pulincisone A-F as well as known chalcone analogs 3,4,2’,4’,6’,7,8-heptahydroxy-7(8)-dihydrochalcone (<b>7</b>) and 4,2’,6’-trihydroxy-4’-methoxydihydrochalcone (<b>8</b>) were isolated from <i>Pulicaria incisa</i> (Lam.) DC. and assayed for cancer preventative activity. Structures were identified by spectroscopic methods, including HRESIMS, 1D and 2D NMR experiments. Pulincisone A and B, are epimers, at stereocenter C-8. A structural revision resulted in pulicisone A (<b>1</b>) and D (<b>4</b>) replacing pulichalconoids B and C, that were previously reported from the same species. Isolated chalcones were assessed for chemopreventive potential as inducers of NAD(P)H: quinone oxidoreductase 1 (NQO1). Compounds <b>2</b>, <b>3</b>, <b>5</b>, and <b>6</b> induced NQO1, using a Prochaska assay. NQO1 protein expression was detected by Western blotting analysis. Compound <b>6</b> among four active compounds had the highest potency as NQO1 inducers. Molecular docking analysis of the NQO1 Keap1 Kelch domain suggests Nrf2-dependent induction. These data indicate that pulincisone F (<b>6</b>) is a promising bioactive antioxidant (NQO1-inducer) with superior docking scores with the Keap1-Nrf2 complex compared to the reference NQO1 inducer sulforaphane (− 8.26 versus − 5.08&#xa0;kcal mol<sup>-</sup>, respectively).</p>

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Chalcone constituents pulincisones A-F isolated from Pulicaria incisa with NQO1 inducer activity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月20日

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  • Ahmed R. Hamed,
  • Tarik A. Mohamed,
  • Sally A. Abdel-Halim,
  • Mohamed H. Abd El-Razek,
  • Sayed A. El-toumy,
  • Maureen Higgins,
  • Krystyna Skalicka-Woźniak,
  • Albena T. Dinkova-Kostova,
  • Paul W. Paré,
  • Mahmoud M. Sakr,
  • Mohamed-Elamir F. Hegazy

摘要

Previously unknown chalcones such as β’-chalcanone-α,β-diols and a β-hydroxydihydrochalcone, named pulincisone A-F as well as known chalcone analogs 3,4,2’,4’,6’,7,8-heptahydroxy-7(8)-dihydrochalcone (7) and 4,2’,6’-trihydroxy-4’-methoxydihydrochalcone (8) were isolated from Pulicaria incisa (Lam.) DC. and assayed for cancer preventative activity. Structures were identified by spectroscopic methods, including HRESIMS, 1D and 2D NMR experiments. Pulincisone A and B, are epimers, at stereocenter C-8. A structural revision resulted in pulicisone A (1) and D (4) replacing pulichalconoids B and C, that were previously reported from the same species. Isolated chalcones were assessed for chemopreventive potential as inducers of NAD(P)H: quinone oxidoreductase 1 (NQO1). Compounds 2, 3, 5, and 6 induced NQO1, using a Prochaska assay. NQO1 protein expression was detected by Western blotting analysis. Compound 6 among four active compounds had the highest potency as NQO1 inducers. Molecular docking analysis of the NQO1 Keap1 Kelch domain suggests Nrf2-dependent induction. These data indicate that pulincisone F (6) is a promising bioactive antioxidant (NQO1-inducer) with superior docking scores with the Keap1-Nrf2 complex compared to the reference NQO1 inducer sulforaphane (− 8.26 versus − 5.08 kcal mol-, respectively).