Anderson Robert F, Yadav Pooja, Patel Deepa, Reynisson Jóhannes, Tipparaju Smitha R, Guise Christopher P, Patterson Adam V, Denny William A, Maroz Andrej, Shinde Sujata S, Hay Michael P
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Org Biomol Chem. 2014 Jun 7;12(21):3386-92. doi: 10.1039/c4ob00236a. Epub 2014 Apr 16.
The radical species underlying the activity of the bioreductive anticancer prodrug, SN30000, have been identified by electron paramagnetic resonance and pulse radiolysis techniques. Spin-trapping experiments indicate both an aryl-type radical and an oxidising radical, trapped as a carbon-centred radical, are formed from the protonated radical anion of SN30000. The carbon-centred radical, produced upon the one-electron oxidation of the 2-electron reduced metabolite of SN30000, oxidises 2-deoxyribose, a model for the site of damage on DNA which leads to double strand breaks. Calculations using density functional theory support the assignments made.
通过电子顺磁共振和脉冲辐解技术，已鉴定出生物还原型抗癌前药SN30000活性背后的自由基种类。自旋捕获实验表明，从SN30000的质子化自由基阴离子形成了芳基型自由基和以碳为中心的自由基形式捕获的氧化自由基。SN30000的双电子还原代谢物经单电子氧化产生的以碳为中心的自由基会氧化2-脱氧核糖，这是DNA损伤位点的模型，可导致双链断裂。使用密度泛函理论进行的计算支持了所做的归属。
