The quantitative structure activity relationship paradigm provides an excellent avenue for investigating ligand–receptor interactions in medicinal chemistry/toxicology. Lateral validation of models formulated using this approach allows for a cohesive understanding of the mechanistic underpinnings of a specific class of related molecules. The diverse biological activities of substituted phenols (X-phenols) in organisms that run the gamut from protozoa to animals are herein examined and compared. Correlations between biological activities and physicochemical attributes of X-phenols reveal strong consistencies between various models. Two parameters in particular, hydrophobicity and electronic terms dominate the extent of interactions between these chemical entities and their molecular targets. Hydrophobicity is represented by π values or partition coefficients while electronic contributions are delineated by molecular orbital indices or Hammett sigma constants. They help us to define the similarity in these mechanistic models that allow for an understanding of forces that are at play at the molecular level.

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Low doses (one-fourth of the LD₅₀) of dichlorvos (DDVP), lambda-cyhalothrin (LMB), cypermethrin (CPM), and imidacloprid (IMP) were administered to adult male Wistar rats for 3 weeks. Erythrocyte antioxidant enzymes, biomarkers of tissue toxicity and histopathology of some visceral organs, were assessed. Glucose-6-phosphate dehydrogenase (G6PD), glutathione-S-transferase (GST), acetylcholine (ACH), and body weight decreased significantly in DDVP- and LMB-treated rats only. However, glutathione (GSH) levels decreased significantly in rats treated with DDVP and IMP. Lipid peroxidation (LPO) increased significantly in plasma of DDVP and erythrocyte of DDVP, CPM, and IMP as compared to the control. Plasma urea and creatinine were insignificant, while aspartate aminotransferase (AST) and alanine amino transferase (ALT) increased significantly in DDVP only; these observations are consistent with the histopathology.

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This study aimed to determine the mode of action of pyflubumide, a novel acaricide under development by Nihon Nohyaku Co., Ltd. Because of its structural similarity to succinate-dehydrogenase inhibitor (SDHI) fungicides, its ability to inhibit mitochondrial complex II was investigated. Pyflubumide exhibited low inhibitory activity on spider mite mitochondria; conversely, its deacylated metabolite (NH-form) showed high mitochondrial inhibitory activity. Pyflubumide was quickly metabolized to its NH-form in the homogenate of spider mites. These results suggest that pyflubumide is a prodrug and that the NH-form is active. Indeed, the NH-form of pyflubumide and the OH-form of cyenopyrafen, a complex II inhibitory acaricide, act on the same enzyme; a double-inhibitor titration assay showed that the binding sites on mitochondrial complex II and/or the manners of binding of these compounds exhibit clear differences. This finding suggests that these two acaricides should be classified into different groups in terms of their mode of action.

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The Aphis gossypii clone, Kushima, which was first discovered in Miyazaki Prefecture, Japan, exhibits significant resistance to neonicotinoid insecticides. We investigated the resistance mechanism involved by sequencing the nicotinic acetylcholine receptor (nAChR) gene, by electrophysiological analysis, and by insecticidal tests in the presence or absence of the oxidase inhibitor, piperonyl butoxide. The Kushima clone showed higher resistance to nitro-substituted neonicotinoids, such as imidacloprid, than to cyano-substituted neonicotinoids, such as acetamiprid. Sequencing of the nAChR subunit genes of a susceptible clone and the Kushima clone revealed an R81T mutation in loop D of the β1 subunit in the resistant clone. This mutation led to a significant shift in the pEC₅₀ value of imidacloprid for the Drosophila melanogaster Dα2-chicken β2 subunit, while it barely affected the concentration-response curves of acetylcholine and acetamiprid.

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