Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Institute of Optical Materials and Technologies "Acad. J. Malinowski", Bulgarian Academy of Sciences, Sofia, Bulgaria.
J Food Biochem. 2021 Jan;45(1):e13584. doi: 10.1111/jfbc.13584. Epub 2020 Dec 19.
The multi-target activity of curcumin makes it a promising pharmacological lead for structural modifications focused on the preparation of new better therapeutics with improved bioavailability. A possible modification is to "decompose" the parent curcumin structure into constituent units and to build up curcumin analogues with biphenyl structural moiety. The antioxidant properties of the so-called "monomers" (m1-m3) and "dimers" (d1-d3) are studied experimentally and computationally. Their protective effects as chain-breaking antioxidants are investigated for the individual compounds and in binary/ternary compositions with α-tocopherol (TOH) and ascorbyl palmitate (AscPH). All monomers manifest significant synergism up to 70% in mixtures with TOH. Synergistic effects are found for the ternary compositions of monomeric analogues upon addition to the binary mixture of standard antioxidants (TOH + AscPH). Dimers with biphenyl skeleton manifest a lower potential in compositions under lipid oxidation conditions. DFT computations provide a detailed insight into the structure and antiradical properties of the curcumin analogues and standard antioxidants. PRACTICAL APPLICATIONS: Bioactive compounds in the diet play a crucial role in the prevention of numerous diseases in whose pathogenesis oxidative stress is well known to be involved. Therefore, enhancement of the antioxidant status of the biological target is often helpful. Two of the monomers studied are considered leading agents in the treatment or prophylaxis of smooth muscle disorders and are useful in the maintenance of the normal gut function- as a calmative for the gut and to ease upset stomach. We hypothesized that the presence of a biphenyl scaffold in the parent molecular structure can enhance the biological activity. Equimolar mixtures of TOH with studied compounds have potential application in food chemistry and medicine. A composition comprising the active agent and additional components (strong conventional antioxidants) may be administered in foodstuffs, as a food supplement, beverage supplement, or as a pharmaceutical composition.
姜黄素的多靶点活性使其成为一种有前途的药理学先导物，可针对其结构进行修饰，旨在制备具有更好生物利用度的新型更好治疗药物。一种可能的修饰方法是将母体姜黄素结构“分解”为组成单元，并构建具有联苯结构部分的姜黄素类似物。实验和计算研究了所谓的“单体”（m1-m3）和“二聚体”（d1-d3）的抗氧化性能。研究了它们作为链断裂抗氧化剂的保护作用，针对单个化合物以及与 α-生育酚（TOH）和抗坏血酸棕榈酸酯（AscPH）的二元/三元组合物进行了研究。所有单体在与 TOH 的混合物中表现出高达 70％的显著协同作用。在向二元标准抗氧化剂混合物（TOH+AscPH）中添加单体类似物的三元组合物时，发现了协同作用。具有联苯骨架的二聚体在脂质氧化条件下的组合物中的潜力较低。DFT 计算为姜黄素类似物和标准抗氧化剂的结构和抗自由基特性提供了详细的见解。实际应用：饮食中的生物活性化合物在预防许多疾病中起着至关重要的作用，在这些疾病的发病机制中，氧化应激众所周知是参与其中的。因此，增强生物靶标的抗氧化状态通常是有帮助的。研究的两种单体被认为是平滑肌疾病治疗或预防的先导药物，并且在维持正常肠道功能方面非常有用-作为肠道的镇静剂，并缓解胃部不适。我们假设母体分子结构中存在联苯支架可以增强生物活性。与研究化合物等摩尔混合物在食品化学和医学中有潜在的应用。包含活性成分和其他成分（强传统抗氧化剂）的组合物可在食品中、作为食品补充剂、饮料补充剂或作为药物组合物进行给药。
