Pulse radiolysis studies of antitumor quinones: radical lifetimes, reactivity with oxygen, and one-electron reduction potentials.
Pulse radiolysis studies of antitumor quinones: radical lifetimes, reactivity with oxygen, and one-electron reduction potentials.
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抗肿瘤醌的脉冲放射分解研究：自由基寿命、与氧的反应性和单电子还原电位。
DOI：
10.1016/0003-9861(81)90263-0
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发表时间：
1981
影响因子：
3.9
通讯作者：
Powis,G
中科院分区：
文献类型：
--
作者：
Svingen,BA;Powis,G
已经通过脉冲放射分解研究了抗肿瘤药物半醌自由基的形成。半醌自由基具有反应性，并且在厌氧条件下的水介质中半衰期短。由阿霉素、丝裂霉素 C 和 2,5-二氮丙啶基-3,6-双(乙氧羰基)胺-1,4-苯醌 (AZQ) 形成的自由基的半衰期分别为 50,100 和 200 μs。半醌自由基的平均扩散距离小于0.6μm。在分子氧存在下，半醌自由基的半衰期缩短。阿霉素半醌与氧快速反应，k= 4.4 × 107m−1s−1。在空气饱和缓冲液中，阿霉素半醌自由基的半衰期可计算为 8 μs，平均扩散距离小于 0.1 μm。如果缓冲液中的半衰期与细胞内的半衰期相当，则半醌自由基必须在其产生生物效应的位点附近产生。测定单电子还原电位(E71)，为AZQ，-168 mV，肾上腺素红，-253 mV，丝裂霉素C，-271 mV，阿霉素，-292 mV，道诺霉素，-305 mV，和蒽二酮，-348 mV。 NADPH-细胞色素P-450还原酶对这些抗肿瘤醌的酶促单电子还原在醌E71的正值更高时增加。
The formation of semiquinone free radicals from antitumor drugs has been studied by pulse radiolysis. The semiquinone free radicals are reactive and have short half-lives in aqueous media under anaerobic conditions. The half-lives of the radicals formed from adriamycin, mitomycin C, and 2,5-diaziridinyl-3,6-bis(carboethoxy)amine-1,4-benzoquinone (AZQ) are 50,100, and 200 μs, respectively. The mean diffusion distance of the semiquinone free radical is less than 0.6 μm. In the presence of molecular oxygen the half-life of the semiquinone free radical is shortened. Adriamycin semiquinone reacts rapidly with oxygen,k= 4.4 × 107m−1s−1. In air-saturated buffer the half-life of adriamycin semiquinone radical can be calculated to be 8 μs with a mean diffusion distance of less than 0.1 μm. If the half-lives in buffer are comparable to those within a cell, semiquinone free radicals must be generated close to the site at which they produce a biological effect. One-electron reduction potentials (E71) were determined and were AZQ, −168 mV, adrenochrome, −253 mV, mitomycin C, −271 mV, adriamycin, −292 mV, daunomycin, −305 mV, and anthracenedione, −348 mV. Enzymatic one-electron reduction of these antitumor quinones by NADPH-cytochromeP-450 reductase increased at more positive values of quinoneE71.