@article{MTMT:36133207, title = {New Insights into the French Paradox: Free Radical Scavenging by Resveratrol Yields Cardiovascular Protective Metabolites}, url = {https://m2.mtmt.hu/api/publication/36133207}, author = {Agbadua, Orinamhe Godwin and Kúsz, Norbert and Berkecz, Róbert and Vass, Elemér and Csámpai, Antal and Tóth, Gábor and Balogh, György Tibor and Marcourt, Laurence and Wolfender, Jean-Luc and Queiroz, Emerson Ferreira and Hunyadi, Attila}, doi = {10.1021/acs.jmedchem.4c03061}, journal-iso = {J MED CHEM}, journal = {JOURNAL OF MEDICINAL CHEMISTRY}, volume = {68}, unique-id = {36133207}, issn = {0022-2623}, abstract = {Resveratrol was subjected to a diversity-oriented synthesis using oxidative transformations by various biorelevant, biomimetic, or biomimetic-related chemical reagents. Using a combined strategy of ultrahigh-resolution profiling, bioactivity screening, and bioactivity-guided isolation, 19 metabolites were obtained. The compounds were tested for their in vitro enzyme inhibitory activity on angiotensin-1 converting enzyme (ACE), cyclooxygenase-1 and -2, and 15-lipoxygenase (LOX), and evaluated for their relevant drug-like properties in silico. The compounds demonstrated a generally increased cardiovascular protective and anti-inflammatory potential and better drug-likeness compared to resveratrol. Trans-δ-viniferin (6) was identified as a competitive, C-domain-selective ACE inhibitor that is over 20 times more potent than resveratrol. Further, trans-ϵ-viniferin (2) acted as an over 40 times stronger LOX inhibitor than resveratrol. While our results cannot be directly translated to the health benefits of dietary resveratrol consumption without further studies, it is demonstrated that biologically relevant oxidative environments transform resveratrol into potent cardiovascular protective and anti-inflammatory metabolites. © 2025 The Authors. Published by American Chemical Society.}, year = {2025}, eissn = {1520-4804}, pages = {10031-10047}, orcid-numbers = {Kúsz, Norbert/0000-0002-9973-6442; Berkecz, Róbert/0000-0002-9076-2177; Vass, Elemér/0000-0001-8898-3846; Csámpai, Antal/0000-0003-2107-7309; Balogh, György Tibor/0000-0003-3347-1880; Marcourt, Laurence/0000-0002-9614-1099; Wolfender, Jean-Luc/0000-0002-0125-952X; Hunyadi, Attila/0000-0003-0074-3472} } @article{MTMT:35499645, title = {Correction: Agbadua et al. Oxidized Resveratrol Metabolites as Potent Antioxidants and Xanthine Oxidase Inhibitors. Antioxidants 2022, 11, 1832}, url = {https://m2.mtmt.hu/api/publication/35499645}, author = {Agbadua, Orinamhe Godwin and Kúsz, Norbert and Berkecz, Róbert and Gáti, Tamás and Tóth, Gábor and Hunyadi, Attila}, doi = {10.3390/antiox13101206}, journal-iso = {ANTIOXIDANTS-BASEL}, journal = {ANTIOXIDANTS}, volume = {13}, unique-id = {35499645}, abstract = {There was an error in the original publication (Section 2.6) [1]: Dry residue of the combined organic layers was purified by preparative HLPC on a biphenyl column with an isocratic elution of CH3CN-H2O (31:69, v/v) to produce compounds 7 (24.80 mg), 8 (13.30 mg), and 9 (33.98 mg) (13.30 mg). Further purification was carried out on the compounds on the same column but using an elution of CH3OH-H2O (52:48, v/v) to obtain compounds 7 (11.93 mg) and 9 (22.62 mg). Compound 8 was further purified by HPLC on a Luna Silica column (250 × 4.6 mm, 5 µm, 100 Å) using an elution of cyclohexane-isopropanol (85:15, v/v) to obtain 8.38 mg of pure compound. A correction has been made to Section 2.6, Reaction with PIFA in Ethanol (Ox4): The dry residue of the combined organic layers was purified by preparative HLPC on a biphenyl column with an isocratic elution of CH3CN-H2O (31:69, v/v) to produce compounds 7 (24.80 mg), 8 (33.98 mg), and 9 (13.30 mg). Further purification was carried out on the compounds on the same column but using an elution of CH3OH-H2O (52:48, v/v) to obtain compounds 7 (11.93 mg) and 8 (22.62 mg). Compound 9 was further purified by HPLC on a Luna Silica column (250 × 4.6 mm, 5 µm, 100 Å) using an elution of cyclohexane-isopropanol (85:15, v/v) to obtain 8.38 mg of pure compound. There was an error in the original publication (Section 2.7) [1]: 2.7. Reaction of Resveratrol with FeCl3 and Oxone in Ethanol (Ox5). A correction has been made to the title of Section 2.7, Reaction of Resveratrol with FeCl3 and Oxone in Ethanol (Ox5): 2.7. Reaction of Resveratrol with Periodic Acid and Oxone in Ethanol (Ox5). There was an error in the original publication (Section 3.2) [1]: Compound 5, i.e., (E)-(±)-2,3-cis-δ-viniferin, is structurally (±)-(E)-5-(3,5-dihydroxystyryl)-3-(3,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)-cis-dihydrobenzofuran. A correction has been made to Section 3.2, Structure Elucidation of the Isolated Compounds, Paragraph Number 5: Compound 5, i.e., (E)-(±)-2,3-trans-δ-viniferin, is structurally (±)-(E)-5-(3,5-dihydroxystyryl)-3-(3,5-dihydroxyphenyl)-2-(4-hydroxyphenyl)-trans-dihydrobenzofuran. There was an error in the original publication (Section 3.2) [1]: Considering the approximately planar structure of the five-membered ring of dihydrobenzofurans, in the cis isomer (compound 5), a dihedral angle close to zero degrees is consistent with a J(H-2,H-3) = 8 Hz coupling. On the other hand, in the case of trans substituents, the detected J(H-2,H-3) = 5 Hz coupling is in accordance with a ≈ 120° dihedral angle (see compound 6). A correction has been made to Section 3.2, Structure Elucidation of the Isolated Compounds, Paragraph Number 5: Even though both compounds 5 and 6 are trans-substituted at the 2,3 positions of the nearly planar dihydrobenzofuran ring, the peri-effect, caused by the 4 substituent of compound 6, alters the geometry of the dominant conformer as compared to that of compound 5. This manifests in differences in the J(H-2,H-3) coupling constants, i.e., 8 Hz and 5 Hz for compounds 5 and 6, respectively. In the original publication [1], there was a mistake in “Figure 1. Structures of resveratrol (1) and its metabolites obtained by chemical oxidation (2–9). Each optically active compound (5, 6, 8, 9) is racemate; for simplicity, only one enantiomer is presented. For compounds 7 and 9, the relative configuration could not be determined” as published. In Section 3.2, the stereochemistry of compound 5 was erroneously assigned as (E)-(±)-2,3-cis-δ-viniferin. The subsequent extensive spectroscopic analysis and high-level in silico quantum chemical calculations revealed this compound as a trans-isomer. The structure and stereochemistry of compound 5 were confirmed by comparing with the 1H-NMR spectroscopic data of trans-δ-viniferin previously reported by Huber and colleagues [2]. Figure 1 should be corrected as follows due to an erroneous additional -OH group added to the structure of 6 in the previously published article. The corrected “Figure 1. Structures of resveratrol (1) and its metabolites obtained by chemical oxidation (2–9). Each optically active compound (5, 6, 8, 9) is racemate; for simplicity, only one enantiomer is presented. For compounds 7 and 9, the relative configuration could not be determined” appears below. In the original publication [1], there was a mistake in “Figure S4. HPLC-PDA fingerprint of oxidized product mixture Ox4” as published. The numbers 8 and 9 were placed wrongly. The corrected “Figure S4. HPLC-PDA fingerprint of oxidized product mixture Ox4” appears below. HPLC-PDA fingerprint of oxidized product mixture Ox4. In the original publication [1], there was a mistake in “Figure S12. Compound 5, HRMS (positive mode)” as published. The structure of 5 needs to be revised. The corrected “Figure S12. Compound 5, HRMS (positive mode)” appears below. Compound 5, HRMS (positive mode). In the original publication [1], there was a mistake in “Figure S28. Compound 5, 1H NMR spectrum, and selROE on δ4.47 and δ5.45 ppm” as published. All stereostructures of compound 5 in Supplementary Figures S28–S32 should be revised. The corrected “Figure S28. Compound 5, 1H NMR spectrum, and selROE on δ4.47 and δ5.45 ppm” appears below. Compound 5, 1H NMR spectrum, and selROE on δ4.47 and δ5.45 ppm. In the original publication [1], there was a mistake in “Figure S29. Compound 5, 13C, APT NMR spectrum” as published. All stereostructures of compound 5 in Supplementary Figures S28–S32 should be revised. The corrected “Figure S29. Compound 5, 13C, APT NMR spectrum” appears below. Compound 5, 13C, APT NMR spectrum. In the original publication [1], there was a mistake in “Figure S30. Compound 5, HSQC spectrum and HSQC section” as published. All stereostructures of compound 5 in Supplementary Figures S28–S32 should be revised. The corrected “Figure S30. Compound 5, HSQC spectrum and HSQC section” appears below. Compound 5, HSQC spectrum and HSQC section. In the original publication [1], there was a mistake in “Figure S31. Compound 5, COSY spectrum” as published. All stereostructures of compound 5 in Supplementary Figures S28–S32 should be revised. The corrected “Figure S31. Compound 5, COSY spectrum” appears below. Compound 5, COSY spectrum. In the original publication [1], there was a mistake in “Figure S32. Compound 5, HMBC spectrum” as published. All stereostructures of compound 5 in Supplementary Figures S28–S32 should be revised. The corrected “Figure S32. Compound 5, HMBC spectrum” appears below. Compound 5, HMBC spectrum. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated. © 2024 by the authors.}, year = {2024}, eissn = {2076-3921}, orcid-numbers = {Kúsz, Norbert/0000-0002-9973-6442; Berkecz, Róbert/0000-0002-9076-2177; Hunyadi, Attila/0000-0003-0074-3472} } @article{MTMT:35156158, title = {Phytochemical Investigation of Carex praecox Schreb. and ACE-Inhibitory Activity of Oligomer Stilbenes of the Plant}, url = {https://m2.mtmt.hu/api/publication/35156158}, author = {Dávid, Csilla Zsuzsanna and Kúsz, Norbert and Agbadua, Orinamhe Godwin and Berkecz, Róbert and Kincses, Annamária and Spengler, Gabriella and Hunyadi, Attila and Hohmann, Judit and Vasas, Andrea}, doi = {10.3390/molecules29143427}, journal-iso = {MOLECULES}, journal = {MOLECULES}, volume = {29}, unique-id = {35156158}, issn = {1431-5157}, abstract = {Phenolic compounds are the main special metabolites of Cyperaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of constituents from Carex praecox. Twenty-six compounds, including lignans, stilbenes, flavonoids, megastigmanes, chromenes, and phenylpropanoids, were identified from the methanol extract of the plant. Five of these compounds, namely, carexines A–E, are previously undescribed natural products. All compounds were isolated for the first time from C. praecox. The ACE-inhibitory activity of seven stilbenoid compounds was tested, and (–)-hopeaphenol proved to be the most active (IC50 7.7 ± 0.9 μM). The enzyme–kinetic studies revealed a mixed-type inhibition; therefore, domain-specific studies were also conducted. The in silico docking of (–)-hopeaphenol to the ACE affirmed some favorable interactions. In addition, the antiproliferative and antibacterial effects of some compounds were also evaluated.}, keywords = {Flavonoids; Lignans; STILBENES; Cyperaceae; ACE-inhibitory activity; Carex praecox}, year = {2024}, eissn = {1420-3049}, orcid-numbers = {Kúsz, Norbert/0000-0002-9973-6442; Berkecz, Róbert/0000-0002-9076-2177; Kincses, Annamária/0000-0002-1591-1419; Spengler, Gabriella/0000-0001-8085-0950; Hunyadi, Attila/0000-0003-0074-3472; Hohmann, Judit/0000-0002-2887-6392; Vasas, Andrea/0000-0002-1818-7702} } @CONFERENCE{MTMT:35150785, title = {French paradox: Exploring the biological relevance of the scavengome of resveratrol}, url = {https://m2.mtmt.hu/api/publication/35150785}, author = {Agbadua, Orinamhe Godwin and Kúsz, Norbert and Berkecz, Róbert and Marton, András and Karancsi, Tamás and Gáti, Tamás and Tóth, Gábor and Balogh, György Tibor and Huber, Robin and Marcourt, Laurence and Wolfender, Jean-Luc and Queiroz, Emerson Ferreira and Hunyadi, Attila}, booktitle = {5th Symposium of Young Researchers on Pharmacognosy : book of abstracts}, doi = {10.14232/syrpharmacognosy.2024.a3}, unique-id = {35150785}, year = {2024}, pages = {8-9}, orcid-numbers = {Kúsz, Norbert/0000-0002-9973-6442; Berkecz, Róbert/0000-0002-9076-2177; Balogh, György Tibor/0000-0001-8273-1760; Huber, Robin/0000-0001-9164-6584; Marcourt, Laurence/0000-0002-9614-1099; Wolfender, Jean-Luc/0000-0002-0125-952X; Queiroz, Emerson Ferreira/0000-0001-9567-1664; Hunyadi, Attila/0000-0003-0074-3472} } @article{MTMT:33709440, title = {Preparation and Evaluation of 6-Gingerol Derivatives as Novel Antioxidants and Antiplatelet Agents}, url = {https://m2.mtmt.hu/api/publication/33709440}, author = {AHMED, Sara Hassan Hassan and Gonda, Tímea and Agbadua, Orinamhe Godwin and Girst, Gábor and Berkecz, Róbert and Kúsz, Norbert and Tsai, Meng-Chun and Wu, Chin-Chung and Balogh, György Tibor and Hunyadi, Attila}, doi = {10.3390/antiox12030744}, journal-iso = {ANTIOXIDANTS-BASEL}, journal = {ANTIOXIDANTS}, volume = {12}, unique-id = {33709440}, abstract = {Ginger (Zingiber officinale) is widely used as a spice and a traditional medicine. Many bioactivities have been reported for its extracts and the isolated compounds, including cardiovascular protective effects. Different pathways were suggested to contribute to these effects, like the inhibition of platelet aggregation. In this study, we synthesised fourteen 6-gingerol derivatives, including eight new compounds, and studied their antiplatelet, COX-1 inhibitor, and antioxidant activities. In silico docking of selected compounds to h-COX-1 enzyme revealed favourable interactions. The investigated 6-gingerol derivatives were also characterised by in silico and experimental physicochemical and blood–brain barrier-related parameters for lead and preclinical candidate selection. 6-Shogaol (2) was identified as the best overall antiplatelet lead, along with compounds 3 and 11 and the new compound 17, which require formulation to optimize their water solubility. Compound 5 was identified as the most potent antioxidant that is also promising for use in the central nervous system (CNS).}, year = {2023}, eissn = {2076-3921}, orcid-numbers = {Berkecz, Róbert/0000-0002-9076-2177; Kúsz, Norbert/0000-0002-9973-6442; Balogh, György Tibor/0000-0003-3347-1880; Hunyadi, Attila/0000-0003-0074-3472} } @{MTMT:33282190, title = {Scavengome of an antioxidant}, url = {https://m2.mtmt.hu/api/publication/33282190}, author = {Hunyadi, Attila and Agbadua, Orinamhe Godwin and Takács, Gergely and Balogh, György Tibor}, booktitle = {Antioxidants}, doi = {10.1016/bs.vh.2022.09.003}, unique-id = {33282190}, year = {2023}, pages = {81-108}, orcid-numbers = {Hunyadi, Attila/0000-0003-0074-3472; Balogh, György Tibor/0000-0003-3347-1880} } @article{MTMT:33233024, title = {Pholiols E–K, lanostane-type triterpenes from Pholiota populnea with anti-inflammatory properties}, url = {https://m2.mtmt.hu/api/publication/33233024}, author = {Yazdani, Morteza and Barta, Anita and Berkecz, Róbert and Agbadua, Orinamhe Godwin and Ványolós, Attila and Hohmann, Judit}, doi = {10.1016/j.phytochem.2022.113480}, journal-iso = {PHYTOCHEMISTRY}, journal = {PHYTOCHEMISTRY}, volume = {205}, unique-id = {33233024}, issn = {0031-9422}, year = {2023}, eissn = {1873-3700}, orcid-numbers = {Yazdani, Morteza/0000-0001-6569-5681; Berkecz, Róbert/0000-0002-9076-2177; Ványolós, Attila/0000-0002-4710-0004; Hohmann, Judit/0000-0002-2887-6392} } @article{MTMT:33686916, title = {6-Gingerol Derivatives as Promising Antiplatelet Leads}, url = {https://m2.mtmt.hu/api/publication/33686916}, author = {Ahmed, SHH and Gonda, Tímea and Agbadua, Orinamhe Godwin and Girst, Gábor and Berkecz, Róbert and Kúsz, Norbert and Tsai, M-C and Wu, C-C and Balogh, György Tibor and Hunyadi, Attila}, doi = {10.1055/s-0042-1759193}, journal-iso = {PLANTA MED}, journal = {PLANTA MEDICA: NATURAL PRODUCTS AND MEDICINAL PLANT RESEARCH}, volume = {88}, unique-id = {33686916}, issn = {0032-0943}, year = {2022}, eissn = {1439-0221}, pages = {1514}, orcid-numbers = {Berkecz, Róbert/0000-0002-9076-2177; Kúsz, Norbert/0000-0002-9973-6442; Balogh, György Tibor/0000-0003-3347-1880; Hunyadi, Attila/0000-0003-0074-3472} } @article{MTMT:33100245, title = {Oxidized Resveratrol Metabolites as Potent Antioxidants and Xanthine Oxidase Inhibitors}, url = {https://m2.mtmt.hu/api/publication/33100245}, author = {Agbadua, Orinamhe Godwin and Kúsz, Norbert and Berkecz, Róbert and Gáti, Tamás and Tóth, Gábor and Hunyadi, Attila}, doi = {10.3390/antiox11091832}, journal-iso = {ANTIOXIDANTS-BASEL}, journal = {ANTIOXIDANTS}, volume = {11}, unique-id = {33100245}, abstract = {Resveratrol is a well-known natural polyphenol with a plethora of pharmacological activities. As a potent antioxidant, resveratrol is highly oxidizable and readily reacts with reactive oxygen species (ROS). Such a reaction not only leads to a decrease in ROS levels in a biological environment but may also generate a wide range of metabolites with altered bioactivities. Inspired by this notion, in the current study, our aim was to take a diversity-oriented chemical approach to study the chemical space of oxidized resveratrol metabolites. Chemical oxidation of resveratrol and a bioactivity-guided isolation strategy using xanthine oxidase (XO) and radical scavenging activities led to the isolation of a diverse group of compounds, including a chlorine-substituted compound (2), two iodine-substituted compounds (3 and 4), two viniferins (5 and 6), an ethoxy-substituted compound (7), and two ethoxy-substitute,0d dimers (8 and 9). Compounds 4, 7, 8, and 9 are reported here for the first time. All compounds without ethoxy substitution exerted stronger XO inhibition than their parent compound, resveratrol. By enzyme kinetic and in silico docking studies, compounds 2 and 4 were identified as potent competitive inhibitors of the enzyme, while compound 2 and the viniferins acted as mixed-type inhibitors. Further, compounds 2 and 9 had better DPPH scavenging activity and oxygen radical absorbing capacity than resveratrol. Our results suggest that the antioxidant activity of resveratrol is modulated by the effect of a cascade of chemically stable oxidized metabolites, several of which have significantly altered target specificity as compared to their parent compound.}, year = {2022}, eissn = {2076-3921}, orcid-numbers = {Kúsz, Norbert/0000-0002-9973-6442; Berkecz, Róbert/0000-0002-9076-2177; Hunyadi, Attila/0000-0003-0074-3472} } @CONFERENCE{MTMT:33100173, title = {Studies on biomimetic oxidized resveratrol metabolite mixtures}, url = {https://m2.mtmt.hu/api/publication/33100173}, author = {Agbadua, Orinamhe Godwin}, booktitle = {3rd Symposium of Young Researchers on Pharmacognosy}, doi = {10.14232/syrpharmacognosy.2022.a2}, unique-id = {33100173}, year = {2022}, pages = {7-7} }