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

TY - JOUR

T1 - Chalcone constituents pulincisones A-F isolated from Pulicaria incisa with NQO1 inducer activity

AU - Hamed, Ahmed R.

AU - Mohamed, Tarik A.

AU - Abdel-Halim, Sally A.

AU - El-Razek, Mohamed H.Abd

AU - El-toumy, Sayed A.

AU - Higgins, Maureen

AU - Skalicka-Woźniak, Krystyna

AU - Dinkova-Kostova, Albena T.

AU - Paré, Paul W.

AU - Sakr, Mahmoud M.

AU - Hegazy, Mohamed Elamir F.

N1 - Copyright: © The Author(s) 2025.

PY - 2025/8/20

Y1 - 2025/8/20

N2 - 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).

AB - 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).

KW - Antioxidant

KW - Asteraceae

KW - Chemopreventive

KW - Dihydrochalcone

KW - NQO1

KW - Pulicaria incisa(Lam.) DC

UR - https://www.scopus.com/pages/publications/105013895396

U2 - 10.1038/s41598-025-15999-2

DO - 10.1038/s41598-025-15999-2

M3 - Article

C2 - 40835884

AN - SCOPUS:105013895396

SN - 2045-2322

VL - 15

JO - Scientific Reports

JF - Scientific Reports

M1 - 30632

ER -