Seyoum Ameha, Asres Kaleab, El-Fiky Fathy Kandeel
Department of Pharmacognosy, School of Pharmacy, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia.
Phytochemistry. 2006 Sep;67(18):2058-70. doi: 10.1016/j.phytochem.2006.07.002. Epub 2006 Aug 17.
The objective of this work is to establish the structural requirements of flavonoids for appreciable radical-scavenging activity (RSA) and elucidate a comprehensive mechanism that can explain their activity. To this end, the RSA of 52 flavonoids against 2,2-diphenyl-1-picrylhydrazyl was determined. The relative change in energy (DeltaH(f)) associated with the formation of various flavonoidal and other phenolic radicals and also the spin distribution in these radicals were determined using computational programmes. By correlating experimental data with DeltaH(f), structural features that affect activity have been identified and considered in perspective. It was shown with compelling evidences that the RSA of flavonoids could be mapped to one of their ring systems, making it possible to study their RSA by dissecting their structures and designing representative simpler models. Consequently, hydroxytoluene units were demonstrated to successfully account for the RSA of flavonoids due to ring B and also to satisfactorily do so for activities due to ring A. Further, a comprehensive model for the radical scavenging reactions of flavonoids (and in general, phenolic compounds), which could account for hydrogen atom donation and the termination of aroxyl radicals, was proposed. Finally, prediction of structural features that could endow flavonoids with appreciable radical scavenging capability was made by considering the stability data and the ease of termination. In conclusion, the underlying molecular phenomena of the RSA of flavonoids could be explained by the ease of hydrogen atom abstraction and the ease of the termination of the flavonoidal aroxyl radicals.
这项工作的目的是确定黄酮类化合物具有可观的自由基清除活性（RSA）的结构要求，并阐明一个能够解释其活性的全面机制。为此，测定了52种黄酮类化合物对2,2-二苯基-1-苦基肼的RSA。使用计算程序确定了与各种黄酮类和其他酚类自由基形成相关的能量相对变化（ΔH(f)）以及这些自由基中的自旋分布。通过将实验数据与ΔH(f)相关联，已确定并从整体上考虑了影响活性的结构特征。有令人信服的证据表明黄酮类化合物的RSA可以映射到其环系之一，从而有可能通过剖析其结构并设计具有代表性的更简单模型来研究它们的RSA。因此，已证明羟基甲苯单元能够成功解释由于B环导致的黄酮类化合物的RSA，并且对于由于A环导致的活性也能令人满意地解释。此外，还提出了一个用于黄酮类化合物（以及一般酚类化合物）自由基清除反应的综合模型，该模型可以解释氢原子的捐赠和芳氧基自由基的终止。最后，通过考虑稳定性数据和终止的难易程度，对能够赋予黄酮类化合物可观自由基清除能力的结构特征进行了预测。总之，黄酮类化合物RSA的潜在分子现象可以通过氢原子提取的难易程度和黄酮类芳氧基自由基终止的难易程度来解释。
