Department of Physical Chemistry, Faculty of Chemistry, Institute of Chemical Science, Maria Curie-Skłodowska University, 20-031 Lublin, Poland.
Doctoral School of Quantitative and Natural Sciences, Maria Curie-Skłodowska University, 20-031 Lublin, Poland.
Molecules. 2022 Jun 3;27(11):3599. doi: 10.3390/molecules27113599.
The micellar liquid chromatography technique and quantitative retention (structure)-activity relationships method were used to predict properties of carbamic and phenoxyacetic acids derivatives, newly synthesized in our laboratory and considered as potential pesticides. Important properties of the test substances characterizing their potential significance as pesticides as well as threats to humans were considered: the volume of distribution, the unbonded fractions, the blood-brain distribution, the rate of skin and cell permeation, the dermal absorption, the binding to human serum albumin, partitioning between water and plants' cuticles, and the lethal dose. Pharmacokinetic and toxicity parameters were predicted as functions of the solutes' lipophilicities and the number of hydrogen bond donors, the number of hydrogen bond acceptors, and the number of rotatable bonds. The equations that were derived were evaluated statistically and cross-validated. Important features of the molecular structure influencing the properties of the tested substances were indicated. The QSAR models that were developed had high predictive ability and high reliability in modeling the properties of the molecules that were tested. The investigations highlighted the applicability of combined chromatographic technique and QS(R)ARs in modeling the important properties of potential pesticides and reducing unethical animal testing.
采用胶束液相色谱技术和定量保留（结构）-活性关系方法，预测了实验室新合成的、被认为具有潜在农药特性的氨基甲酸酯和苯氧乙酸衍生物的性质。考虑了测试物质的重要性质，这些性质表明了它们作为农药的潜在重要性以及对人类的威胁：分布容积、非键部分、血脑分布、皮肤和细胞渗透性、皮肤吸收、与人血清白蛋白的结合、水与植物角质层之间的分配以及致死剂量。药代动力学和毒性参数被预测为溶质脂溶性以及氢键供体、氢键受体和可旋转键的数量的函数。所得到的方程在统计学上进行了评估和交叉验证。指出了影响测试物质性质的分子结构的重要特征。所开发的 QSAR 模型在预测测试分子的性质方面具有很高的预测能力和可靠性。这些研究强调了组合色谱技术和 QSARs 在模拟潜在农药重要性质和减少不道德动物试验方面的适用性。
