CIQ/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto 4169-007, Portugal.
Eur J Med Chem. 2013 Apr;62:289-96. doi: 10.1016/j.ejmech.2012.12.049. Epub 2013 Jan 8.
Phenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neurodegenerative disorders. However, until now, most of natural antioxidants have limited therapeutic success a fact that could be related with their limited distribution throughout the body and with the inherent difficulties to attain the target sites. The development of phenolic antioxidants based on a hybrid concept and structurally based on natural hydroxybenzoic (gallic acid) and hydroxycinnamic (caffeic acid) scaffolds seems to be a suitable solution to surpass the mentioned drawbacks. Galloyl-cinnamic hybrids were synthesized and their antioxidant activity as well as partition coefficients and redox potentials evaluated. The structure-property-activity relationship (SPAR) study revealed the existence of a correlation between the redox potentials and antioxidant activity. The galloyl-cinnamic acid hybrid stands out as the best antioxidant supplementing the effect of a blend of gallic acid plus caffeic acid endorsing the hypothesis that the whole is greater than the sum of the parts. In addition, some hybrid compounds possess an appropriate lipophilicity allowing their application as chain-breaking antioxidant in biomembranes or other type of lipidic systems. Their predicted ADME properties are also in accordance with the general requirements for drug-like compounds. Accordingly, these phenolic hybrids can be seen as potential antioxidants for tackling the oxidative status linked to the neurodegenerative, inflammatory or cancer processes.
酚酸是无处不在的抗氧化剂，约占我们饮食中酚类化合物的三分之一。流行病学研究支持了它们的重要性，这些研究表明，饮食中摄入酚类抗氧化剂与癌症和神经退行性疾病等疾病的发生呈负相关。然而，到目前为止，大多数天然抗氧化剂的治疗效果有限，这一事实可能与其在体内的有限分布以及难以到达靶位有关。基于混合概念和结构上基于天然羟基苯甲酸（没食子酸）和羟基肉桂酸（咖啡酸）支架的酚类抗氧化剂的开发似乎是克服上述缺点的合适解决方案。合成了没食子酰肉桂酸杂化物，并评估了它们的抗氧化活性、分配系数和氧化还原电位。结构-性质-活性关系（SPAR）研究表明，氧化还原电位与抗氧化活性之间存在相关性。没食子酰肉桂酸杂化物是一种很好的抗氧化补充剂，可增强没食子酸加咖啡酸混合物的作用，证实了整体大于部分之和的假设。此外，一些杂化物具有适当的亲脂性，允许它们作为生物膜或其他类型的脂质系统中的链断裂抗氧化剂应用。它们预测的 ADME 性质也符合类药化合物的一般要求。因此，这些酚类杂化物可以被视为用于解决与神经退行性、炎症或癌症过程相关的氧化应激的潜在抗氧化剂。
