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Structure-Activity Relationship (SAR) and in vitro Predictions of Mutagenic and Carcinogenic Activities of Ixodicidal Ethyl-Carbamates
BioMed Research International ( IF 2.6 ) Pub Date : 2020-11-21 , DOI: 10.1155/2020/2981681
María G. Prado-Ochoa 1 , Maribel Strassburger-Madrigal 2 , Rafael Camacho-Carranza 3 , Jesús J. Espinosa-Aguirre 3 , Ana M. Velázquez-Sánchez 4 , Victor H. Vázquez-Valadez 4 , Enrique Angeles 4 , Fernando Alba-Hurtado 1 , Marco A. Muñoz-Guzmán 1
Affiliation  

Ethyl-4-bromophenyl-carbamate (LQM 919) and Ethyl-4-chlorophenyl-carbamate (LQM 996) are compounds that inhibit egg-laying and hatching of tick larvae that are resistant to conventional ixodicides. The structure-activity relationship (SAR) to get the endpoint predictions of mutagenicity and carcinogenicity of the LQM 919 and LQM 996 was performed and the absence of mutagenicity was confirmed by Ames test. SAR analysis show no structural alerts indicating the ability of ethyl-carbamates to bind biomolecules or estrogen receptors. Endpoint of mutagenicity with and without metabolic activation showed that the ethyl-carbamates were negative (p <0.05) for mutagenicity induction in strains TA97, TA98, TA102, TA1535, TA1537 and TA1538 of Salmonella typhimurium. Pre-incubation with different ethyl-carbamate concentrations did not increase the number of spontaneously reverting colonies; moreover, the compounds did not induce a concentration-dependent increase in the number of reverting colonies in any of the strains used. This confirmed the absence of mutagenic activity in this test system. Exogenous metabolic activation did not modify these observations; suggesting that no metabolites with mutagenic activity were present. The endpoint of carcinogenicity in rats were negative for LQM 919 (p <0.05,) and LQM 996 (p <0.001). The results of the present study strongly suggest that ethyl-carbamates do not represent a risk for cancer in mammals.

中文翻译:

结构活性关系(SAR)和杀虫环乙基氨基甲酸酯致突变和致癌活性的体外预测。

4-溴苯基氨基甲酸乙酯(LQM 919)和-4-氯苯基氨基甲酸乙酯(LQM 996)是抑制tick虫幼虫产卵和孵化的化合物,这些幼虫对常规的杀螨剂有抵抗力。进行结构-活性关系(SAR)以得出LQM 919和LQM 996的致突变性和致癌性的终点预测,并通过Ames试验确认不存在致突变性。SAR分析显示没有结构警报表明氨基甲酸乙酯具有结合生物分子或雌激素受体的能力。有和没有代谢活化的致突变性终点表明,氨基甲酸乙酯对鼠伤寒沙门氏菌TA97,TA98,TA102,TA1535,TA1537和TA1538菌株的致突变性诱导呈阴性(p <0.05)。用不同浓度的氨基甲酸乙酯预孵育不会增加自发回复菌落的数量。此外,该化合物在任何所用菌株中均未引起回复菌落数量的浓度依赖性增加。这证实了该测试系统中不存在诱变活性。外源性代谢激活并没有改变这些观察结果。这表明不存在具有诱变活性的代谢产物。大鼠的致癌性终点为LQM 919(p <0.05,)和LQM 996(p <0.001)为阴性。本研究的结果有力地表明,氨基甲酸乙酯不代表哺乳动物患癌症的风险。
更新日期:2020-11-22
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