Structure-Activity Relationship Investigation on Reaction Mechanism between Chlorinated Quinoid Carcinogens and Clinically-Used Aldoxime Nerve-Agent Antidote under Physiological Condition
文献类型：期刊论文
| 作者 | Xie, Lin-Na; Huang, Chun-Hua; Xu, Dan; Qin, Li; Li, Feng ; Shan, Guo-Qiang; Liu, Zhi-Sheng; Cao, Dong; Geng, Fang-Lan; Mao, Li
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| 刊名 | CHEMICAL RESEARCH IN TOXICOLOGY
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| 出版日期 | 2021-04-19 |
| 卷号 | 34期号:4页码:1091-1100 |
| ISSN号 | 0893-228X |
| 英文摘要 | Pyridinium aldoximes are best-known therapeutic antidotes used for clinical treatment of poisonings by organophosphorus nerve-agents and pesticides. Recently, we found that pralidoxime (2-PAM, a currently clinically used nerve-agent antidote) could also detoxify tetrachloro-1,4-benzoquinone (TCBQ), which is a carcinogenic quinoid metabolite of the widely used wood preservative pentachlorophenol under normal physiological conditions, via an unusually mild and facile Beckmann fragmentation mechanism accompanied by radical homolysis. However, it is not clear whether the less-chlorinated benzoquinones (C(n)BQs, n <= 3) act similarly; if so, what is the structure-activity relationship? In this study, we found that (1) The stability of reaction intermediates produced by different C(n)BQs and 2-PAM was dependent not only on the position but also the degree of Cl-substitution on C(n)BQs, which can be divided into TCBQ and DCBQ (dichloro-1,4-benzoquinone)-subgroup; (2) The pK a value of hydroxlated quinones (C(n-1)BQ-OHs, the hydrolysis products of C(n)BQA determined the stability of corresponding intermediates, that is, the decomposition rate of the intermediates depended on the acidity of C(n-1)BQ-OHs; (3) The pK, value of the corresponding C(n-1)BQ-OHs could also determine the reaction ratio of Beckmann fragmentation to radical homolysis in C(n)BQ5/2-PAM. These new findings on the structure-activity relationship of the halogenated quinoid carcinogens detoxified by pyridinium aldoxime therapeutic agents via Beckmann fragmentation and radical homolysis reaction may have broad implications on future biomedical and environmental research. |
| WOS研究方向 | Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Toxicology |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/45846]  |
| 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 |
| 作者单位 | 1.Chinese Ctr Dis Control & Prevent, Natl Inst Environm Hlth, China CDC Key Lab Environm & Populat Hlth, Beijing 100021, Peoples R China 2.Hong Kong Baptist Univ, Hong Kong, Peoples R China 3.Res Ctr Ecoenvironm Sci, Joint Inst Environm Sci, Beijing, Peoples R China 4.Nankai Univ, Coll Environm Sci & Engn, Key Lab Pollut Proc & Environm Criteria,Minist Ed, Tianjin Key Lab Environm Rem 5.Zhejiang Chinese Med Univ, Sch Basic Med Sci & Publ Hlth, Hangzhou 310053, Peoples R China 6.Univ Chinese Acad Sci, State Key Lab Environm Chem & Ecotoxicol, Res Ctr Ecoenvironm Sci, Beijing 100085, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Lin-Na,Huang, Chun-Hua,Xu, Dan,et al. Structure-Activity Relationship Investigation on Reaction Mechanism between Chlorinated Quinoid Carcinogens and Clinically-Used Aldoxime Nerve-Agent Antidote under Physiological Condition[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2021,34(4):1091-1100. |
| APA | Xie, Lin-Na.,Huang, Chun-Hua.,Xu, Dan.,Qin, Li.,Li, Feng.,...&Zhu, Ben-Zhan.(2021).Structure-Activity Relationship Investigation on Reaction Mechanism between Chlorinated Quinoid Carcinogens and Clinically-Used Aldoxime Nerve-Agent Antidote under Physiological Condition.CHEMICAL RESEARCH IN TOXICOLOGY,34(4),1091-1100. |
| MLA | Xie, Lin-Na,et al."Structure-Activity Relationship Investigation on Reaction Mechanism between Chlorinated Quinoid Carcinogens and Clinically-Used Aldoxime Nerve-Agent Antidote under Physiological Condition".CHEMICAL RESEARCH IN TOXICOLOGY 34.4(2021):1091-1100. |
入库方式： OAI收割
来源：生态环境研究中心
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