Unexpected activation of N-alkyl hydroxamic acids to produce reactive N-centered free radicals and DNA damage by carcinogenic chlorinated quinones under normal physiological conditions
文献类型：期刊论文
| 作者 | Huang, Chun-Hua; Xu, Dan; Qin, Li; Tang, Tian-Shu; Shan, Guo-Qiang; Xie, Lin-Na; Li, Pei-Lin; Mao, Li; Shao, Jie; Zhu, Ben-Zhan |
| 刊名 | FREE RADICAL BIOLOGY AND MEDICINE
 |
| 出版日期 | 2020-01 |
| 卷号 | 146页码:70-78 |
| 关键词 | N-alkyl hydroxamic acids N-centered radicals Chlorinated quinones Carbon-nitrogen bonding conjugate DNA adducts |
| ISSN号 | 0891-5849 |
| 英文摘要 | We found recently that benzohydroxamic acid (BHA) could detoxify the chlorinated quinoid carcinogens via an unusual Lossen rearrangement reaction. However, it is not clear what would happen when the nitrogen hydrogen of BHA was substituted with methyl and other alkyl groups. Here we show that N-methyl benzohydroxamic acid (N-MeBHA, a simple model compound for the classic iron-chelator deferoxamine, which is a typical N-alkyl trihydroxamic acid) could react with 2,5-dichloro-1,4-benzoquinone (DCBQ) to form a relatively stable initial carbon-oxygen bonding conjugation intermediate CBQ-O-N-MeBHA. However, the major final product was identified, unexpectedly, as a carbon-nitrogen bonding conjugate CBQ(OH)-N(CH3)-COAr, which is the rearranged isomer of CBQ-O-N-MeBHA. Interestingly, a new 18-line nitrogen-centered radical and a carbon-centered quinone ketoxy radical were observed by the ESR spin-trapping method, which was further confirmed by HPLC-MS and N-15-isotope labeling methods. We further found that both new DNA adducts and DNA strand breaks could be produced by the reactive nitrogen-centered radical. Taken together, we propose that the reaction between DCBQ and N-MeBHA was not via the Lossen rearrangement, but rather through a novel radical homolysis and recoupling pathway. Analogous results were observed for other chlorinated quinones and N-alkyl hydroxamic acids including the widely-used trihydroxamate iron-chelating drug deferoxamine. This represents the first report of unexpected radical pathway for the reaction between chlorinated quinones and N-alkyl hydroxamic acids under normal physiological conditions, which may have broad biological and environmental significance for future study of carcinogenic chloroquinones and hydroxamic acid drugs. |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/44849]  |
| 专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
| 推荐引用方式 GB/T 7714 | Huang, Chun-Hua,Xu, Dan,Qin, Li,et al. Unexpected activation of N-alkyl hydroxamic acids to produce reactive N-centered free radicals and DNA damage by carcinogenic chlorinated quinones under normal physiological conditions[J]. FREE RADICAL BIOLOGY AND MEDICINE,2020,146:70-78. |
| APA | Huang, Chun-Hua.,Xu, Dan.,Qin, Li.,Tang, Tian-Shu.,Shan, Guo-Qiang.,...&Zhu, Ben-Zhan.(2020).Unexpected activation of N-alkyl hydroxamic acids to produce reactive N-centered free radicals and DNA damage by carcinogenic chlorinated quinones under normal physiological conditions.FREE RADICAL BIOLOGY AND MEDICINE,146,70-78. |
| MLA | Huang, Chun-Hua,et al."Unexpected activation of N-alkyl hydroxamic acids to produce reactive N-centered free radicals and DNA damage by carcinogenic chlorinated quinones under normal physiological conditions".FREE RADICAL BIOLOGY AND MEDICINE 146(2020):70-78. |
入库方式： OAI收割
来源：生态环境研究中心
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