In vitro inhibition of human red blood cell acetylcholinesterase (AChE) by temephos-oxidized products
In vitro inhibition of human red blood cell acetylcholinesterase (AChE) by temephos-oxidized products
复制标题
DOI：
10.1038/s41598-019-51261-2
复制
发表时间：
2019-10-14
影响因子：
4.6
通讯作者：
Sierra-Santoyo, Adolfo
中科院分区：
文献类型：
--
作者：
Alberto Verdin-Betancourt, Francisco;Figueroa, Mario;Sierra-Santoyo, Adolfo
Temephos（Tem）是一种有机磷农药，广泛用于杀死和防止传播登革热、寨卡和基孔肯雅病毒的主要媒介的生长。在氯化水中，Tern被氧化成其二氧杂环砜（Tern-dox-SO）、二氧杂环砜（Tern-dox-SO 2）和亚砜（Tern-SO）衍生物;然而，这些化合物无法在商业上用作标准品和毒理学研究。在本研究中，我们合成并表征了TEM-氧化产物和化合物4，4 '-亚磺酰基联苯酚。这些化合物是由Tem或4，4 '-硫代联二酚与次氯酸钠或高碘酸钾反应得到的，并通过IR，NMR和UPLC-H RESIMS进行了表征。体外评价Tem-dox-SO_2氧化产物对人红细胞乙酰胆碱酯酶（RBC AChE）的抑制效力表明，Tem-dox-SO_2是最有效的人红细胞AChE抑制剂，其作用比典型的AChE抑制剂乙基对氧磷更明显。建立了Tem代谢产物的HPLC-DAD分析方法，可用于生物和环境样品中Tem的监测。Tern氧化代谢产物抑制人红细胞乙酰胆碱酯酶的能力表明，在氯化饮用水中加入Tern可能会导致暴露后红细胞乙酰胆碱酯酶抑制的风险增加。
Temephos (Tem) is an organophosphorus pesticide widely used to kill and prevent the growth of the main vectors for the transmission of dengue, zika, and chikungunya viruses. In chlorinated water, Tern is oxidized to its dioxon-sulfoxide (Tern-dox-SO), dioxon-sulfone (Tern-dox-SO2), and sulfoxide (Tern-SO) derivatives; however, these compounds are not commercially available to be used as standards and in toxicological studies. In the present study, we synthesized and characterized the Tem-oxidation products and the compound 4,4'-sulfinyldiphenol. These compounds were obtained by a simple reaction between Tem or 4,4'-thiodiphenol with sodium hypochlorite or potassium periodate, and were characterized by IR, NMR, and U PLC-H RESIMS. The in vitro evaluation of inhibitory potency of Tem-oxidized products on human red blood cell acetylcholinesterase (RBC AChE) showed that Tem-dox-SO2 was the most potent inhibitor of human RBC AChE, and its effect was more pronounced than that observed for ethyl-paraoxon, a potent typical inhibitor of AChE. An HPLC-DAD method for the analysis of metabolic products of Tem was developed, which may be useful for monitoring in biological and environmental samples. The ability of Tern-oxidized metabolites to inhibit human RBC AChE suggests that the addition of Tern to chlorinated drinking water could result in an increase in the risk of RBC AChE inhibition after exposure.