Abstract

In an attempt to obtain the modified and novel insecticides with low human toxicity, a series of novel mono-, bis-, and tetraphosphonic acid derivatives were designed and characterized by infrared, ¹H, ¹³C, and ³¹P NMR spectroscopy and X-ray crystallography. The inhibitory effects of the synthesized compounds were evaluated using the in vitro Ellman method on human and insect acetylcholinesterase (AChE). Some of these compounds, which had low human and high insect toxicity, were chosen to assess the killing effects (in vivo) on third larval instar of elm leaf beetle (X. luteola). In vivo and in vitro evidence has revealed that bisphosphonic acids, containing hydrophobic systems, have a good selectivity of insect AChE inhibition. In the present study, docking results showed that bisphosphonic acids had lower binding energy and higher inhibition compared with tetraphosphonic acids due to the type of their topology and the ability of their hydrogen to interact with the catalytic triad (the main active site of the enzyme). Additionally, the QSAR results demonstrated that the major effecting factors on the insecticidal activity of the subject compounds are the hydrophobicity, size, shape, and ability to form a hydrogen bond. The present study can be helpful in the development of new insecticides.

Graphic abstract

中文翻译：

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新膦酸的合成、晶体结构、胆碱酯酶抑制活性、杀虫活性评估和计算研究

摘要

为了获得对人体毒性低的改良新型杀虫剂，设计了一系列新型单膦酸、双膦酸和四膦酸衍生物，并对其进行红外、¹ H、¹³ C和^31表征。P NMR光谱和X射线晶体学。使用体外 Ellman 方法评估合成化合物对人和昆虫乙酰胆碱酯酶 (AChE) 的抑制作用。选择其中一些具有低人类毒性和高昆虫毒性的化合物来评估（体内）对榆叶甲虫（X. luteola）第三龄幼虫的杀灭作用。体内和体外证据表明，含有疏水系统的双膦酸对昆虫 AChE 抑制具有良好的选择性。在本研究中，对接结果表明，与四膦酸相比，双膦酸具有较低的结合能和较高的抑制作用，这是由于其拓扑结构的类型及其氢与催化三联体（酶的主要活性位点）相互作用的能力。 . 此外，QSAR结果表明，影响目标化合物杀虫活性的主要因素是疏水性、大小、形状和形成氢键的能力。本研究有助于开发新的杀虫剂。

图形摘要