Quantitative Retention (Structure)–Activity Relationships in Predicting the Pharmaceutical and Toxic Properties of Potential Pesticides

Abstract

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.

Over-Pressured Layer Chromatography and QSARs in predicting pharmacokinetics and toxicity of new herbicide candidates

“…The results obtained are internally consistent -greater binding of a substance to albumin (log KHSA and %PPB) implies a decrease in the amount of its unbound fraction in plasma. Additionally, lipophilicity also decreases the concentration of the free fraction in the brain (fu, brain) as shown in Figure 2 (Janicka & Śliwińska 2022).…”

“…In the case of intravenous administration, both lipophilicity and polarizability of the substance are equally important. However, for intraperitoneal administration, the parameter value is mainly determined by its polarizability (Janicka & Śliwińska 2022).…”

“…Based on this knowledge (Collander 1951;Kaliszan 1987), the relationship between partitioning log Po/w and chromatographic log k parameters can be determined as: log 𝑃 𝑜/𝑤 = 𝑎 log 𝑘 + 𝑐𝑜𝑛𝑠𝑡 (3) The retention factor log k, as presented in Equation (3), can correspond to various chromatographic techniques and systems. For example, log kw values determined by RP HPLC column technique (using water as the mobile phase) or analogous RM0 parameters in thin-layer chromatography (TLC) (Biagi et al 1994;Janicka et al 2022aJanicka et al , 2022bJanicka & Śliwińska 2022). This parameter can also be determined in chromatographic systems that mimic biological partitioning, such as immobilized artificial membranes (IAMs) or columns with immobilized cholesterol, glycoproteins, human or rat serum albumins, and others.…”

Exploration of 2D and 3D-QSAR analysis and docking studies for novel dihydropteridone derivatives as promising therapeutic agents targeting glioblastoma

“…To facilitate the efficient design and evaluation of novel drugs, we introduce computer-aided drug design, with quantitative structure-activity relationship (QSAR) being the most exceptional experimental approach ( Janicka and Śliwińska, 2022 ). This mathematical framework establishes a correlation between the scrutiny of structural attributes and the corresponding pharmacological efficacy.…”