Agbadua Orinamhe G, Kúsz Norbert, Berkecz Róbert, Vass Elemér, Csámpai Antal, Tóth Gábor, Balogh György T, Marcourt Laurence, Wolfender Jean-Luc, Queiroz Emerson Ferreira, Hunyadi Attila
Institute of Pharmacognosy, University of Szeged, Eötvös str. 6, H-6720 Szeged, Hungary.
Institute of Pharmaceutical Analysis, University of Szeged, Somogyi str. 4, H-6720 Szeged, Hungary.
J Med Chem. 2025 May 22;68(10):10031-10047. doi: 10.1021/acs.jmedchem.4c03061. Epub 2025 May 7.
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 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 . The compounds demonstrated a generally increased cardiovascular protective and anti-inflammatory potential and better drug-likeness compared to resveratrol. -δ-viniferin () was identified as a competitive, C-domain-selective ACE inhibitor that is over 20 times more potent than resveratrol. Further, -ε-viniferin () 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.
白藜芦醇通过各种与生物相关、仿生或仿生相关的化学试剂进行氧化转化，进行了多样化导向合成。采用超高分辨率分析、生物活性筛选和生物活性导向分离相结合的策略，获得了19种代谢产物。测试了这些化合物对血管紧张素-1转换酶（ACE）、环氧化酶-1和-2以及15-脂氧合酶（LOX）的酶抑制活性，并评估了它们相关的类药物性质。与白藜芦醇相比，这些化合物总体上显示出增强的心血管保护和抗炎潜力以及更好的类药物性质。-δ-葡萄素（）被鉴定为一种竞争性的、C结构域选择性ACE抑制剂，其效力比白藜芦醇高20倍以上。此外，-ε-葡萄素（）作为一种LOX抑制剂，其效力比白藜芦醇强40倍以上。虽然在没有进一步研究的情况下，我们的结果不能直接转化为食用膳食白藜芦醇对健康的益处，但已证明与生物相关的氧化环境可将白藜芦醇转化为有效的心血管保护和抗炎代谢产物。
