Research Analytics Team, Analytical Department, Łukasiewicz Research Network-Industrial Chemistry Institute, 8 Rydygiera Street, 01-793 Warsaw, Poland.
Faculty of Chemistry, Jagiellonian University, 2 Gronostajowa Street, 30-387 Krakow, Poland.
Int J Mol Sci. 2021 Aug 16;22(16):8783. doi: 10.3390/ijms22168783.
Pharmacological and nutraceutical effects of isoflavones, which include genistein (GE), are attributed to their antioxidant activity protecting cells against carcinogenesis. The knowledge of the oxidation mechanisms of an active substance is crucial to determine its pharmacological properties. The aim of the present work was to explain complex oxidation processes that have been simulated during voltammetric experiments for our new thiolated genistein analog (TGE) that formed the self-assembled monolayer (SAM) on the gold electrode. The thiol linker assured a strong interaction of sulfur nucleophiles with the gold surface. The research comprised of the study of TGE oxidative properties, IR-ATR, and MALDI-TOF measurements of SAM before and after electrochemical oxidation. TGE has been shown to be electrochemically active. It undergoes one irreversible oxidation reaction and one quasi-reversible oxidation reaction in PBS buffer at pH 7.4. The oxidation of TGE results in electroactive products composed likely from TGE conjugates (e.g., trimers) as part of polymer. The electroactive centers of TGE and its oxidation mechanism were discussed using IR supported by quantum chemical and molecular mechanics calculations. Preliminary in-vitro studies indicate that TGE exhibits higher cytotoxic activity towards DU145 human prostate cancer cells and is safer for normal prostate epithelial cells (PNT2) than genistein itself.
异黄酮（包括染料木黄酮）的药理学和营养作用归因于其抗氧化活性，可保护细胞免受致癌作用。了解活性物质的氧化机制对于确定其药理特性至关重要。本工作的目的是解释在针对我们新的巯基化染料木黄酮类似物（TGE）的伏安实验中模拟的复杂氧化过程，该类似物在金电极上形成了自组装单层（SAM）。硫醇接头确保了硫亲核试剂与金表面的强相互作用。研究包括 TGE 氧化性质的研究、IR-ATR 和电化学氧化前后 SAM 的 MALDI-TOF 测量。已经证明 TGE 具有电化学活性。在 pH 7.4 的 PBS 缓冲液中，它经历了一个不可逆的氧化反应和一个准可逆的氧化反应。TGE 的氧化导致电活性产物，可能由 TGE 缀合物（例如三聚体）组成，作为聚合物的一部分。使用量子化学和分子力学计算支持的 IR 讨论了 TGE 的电活性中心及其氧化机制。初步的体外研究表明，TGE 对人前列腺癌 DU145 细胞表现出更高的细胞毒性活性，并且比染料木黄酮本身对正常前列腺上皮细胞（PNT2）更安全。
