CIQ/Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto 4169-007, Portugal.
Mitochondrion. 2013 Sep;13(5):427-35. doi: 10.1016/j.mito.2012.12.002. Epub 2012 Dec 13.
The therapeutic potential of natural phenolic antioxidants in human diseases associated with oxidative damage has received great attention to date. Appraisal of literature evidences that, in general, antioxidant therapy has enjoyed relative successes in preclinical studies but little benefits in human intervention studies or clinical trials. In fact, despite the huge, largely untapped potential therapeutic benefit of natural phenolic antioxidants, such as vitamins, non-flavonoid and flavonoid compounds, they appear not to be suitable drug candidates. The problem may be related, among others, to their non-drug-likeness properties. Though controversial the results obtained so far confirm the importance of exploring phenolic natural systems as safe templates for the design of new antioxidants. To support the assumption an outlook of the lead structural optimization process to improve ADME properties was given by means of natural hydroxycinnamic acids as a case study. The optimization of drug physicochemical properties and the development of appropriate delivery antioxidant systems can provide in the next future a way out to attain effective therapeutic antioxidant agents.
迄今为止，天然酚类抗氧化剂在与氧化损伤相关的人类疾病中的治疗潜力引起了广泛关注。评估文献表明，一般来说，抗氧化治疗在临床前研究中取得了相对成功，但在人体干预研究或临床试验中获益甚微。事实上，尽管天然酚类抗氧化剂（如维生素、非类黄酮和类黄酮化合物）具有巨大的、尚未开发的潜在治疗益处，但它们似乎不适合作为候选药物。问题可能与它们的非药物特性等有关。尽管目前的结果存在争议，但它们证实了探索酚类天然系统作为新型抗氧化剂设计安全模板的重要性。为了支持这一假设，通过天然羟基肉桂酸作为案例研究，展望了改善 ADME 性质的先导结构优化过程。通过优化药物物理化学性质和开发适当的抗氧化剂传递系统，可以为未来开发有效的治疗性抗氧化剂提供出路。
