Candeias L P, Everett S A, Wardman P
Cancer Research Campaign Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, UK.
Free Radic Biol Med. 1993 Oct;15(4):385-94. doi: 10.1016/0891-5849(93)90038-v.
The sulphate radical (SO4.-), a model one-electron oxidant, reacts with the antitumour drug flavone-8-acetic acid (FFA) with the rate constant 9.1 x 10(8) dm3mol-1s-1 to yield an uncharged radical that reacts with oxygen (k approximately 1 x 10(9) dm3mol-1s-1). The oxidation of FAA by SO4.- in a steady-state system was found to release carbon dioxide with a yield of 96% relative to that of the SO.4-. The results are interpreted by fast (t1/2 < or = 1 microsecond) and efficient decarboxylation of the FAA radical cation, resulting in a carbon-centred radical. The reaction of the latter with oxygen is a possible source of radical-driven cytotoxic pathways, such as singlet oxygen formation via the Russell mechanism or H-abstraction from lipids. On the basis of the observations in the model system, a possible free radical mechanism for the antitumour action of the drug is suggested.
硫酸根自由基（SO4.-）是一种典型的单电子氧化剂，它与抗肿瘤药物黄酮 - 8 - 乙酸（FFA）反应，反应速率常数为9.1×10(8) dm3mol-1s-1，生成一种不带电荷的自由基，该自由基与氧气反应（速率常数k约为1×10(9) dm3mol-1s-1）。发现在稳态体系中，SO4.-对FFA的氧化作用释放出二氧化碳，其产率相对于SO4.-为96%。这些结果可通过FFA自由基阳离子的快速（半衰期t1/2≤1微秒）且高效的脱羧作用来解释，从而产生以碳为中心的自由基。后者与氧气的反应可能是自由基驱动的细胞毒性途径的一个来源，例如通过拉塞尔机制形成单线态氧或从脂质中夺取氢原子。基于模型体系中的观察结果，提出了该药物抗肿瘤作用的一种可能的自由基机制。
