Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either mAChE or hAChE, to predict the listed pesticides’ binding modes. Calculated energies of global minima (E_{glob_min}) and free energies of binding (∆G_binding) were correlated with the pesticides’ acute toxicities (i.e., the LD₅₀ values) against mice, as well to generate the model that could predict the LD₅₀s against humans. Although for most of the pesticides the low E_{glob_min} correlates with the high acute toxicity, it is the ∆G_binding that conditions the LD₅₀ values for all the evaluated pesticides. Derived pLD₅₀ = f(∆G_binding) mAChE model may predict the pLD₅₀ against hAChE, too. The hAChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.

This paper summarises the results of voltammetric studies on the herbicide 3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea (Linuron), using a carbon paste electrode containing tricresyl phosphate (TCP-CPE) as liquid binder. The principal experimental conditions, such as the pH effect, investigated in Britton-Robinson buffer solutions (pH 2.0–7.0), the peak characteristics for the analyte of interest, or instrumental parameters for the differential pulse voltammetric mode were optimized for the method. As found out, the best electroanalytical performance of the TCP-CPE was achieved at pH 2.0, whereby the oxidation peak of Linuron appeared at ca. +1.3 V vs. SCE. The analytical procedure developed offers good linearity in the concentration range of 1.25–44.20 μg mL⁻¹ (1.77 × 10⁻⁴–5.05 × 10⁻⁶ mol L⁻¹), showing - for the first time - the applicability of the TCP-CPE for anodic oxidations in direct voltammetry (without accumulation). The method was then verified by determining Linuron in a spiked river water sample and a commercial formulation and the results obtained agreed well with those obtained by the reference HPLC/UV determination.

Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PL^pro inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin D was selected as a peptide drug, showing the best in silico interaction profile with PL^pro. After the expression and purification of PL^pro, gramicidin D was screened for protease inhibition in vitro and was found to be active against PL^pro. The current study’s findings are significant because it is critical to identify COVID-19 therapies that are efficient, affordable, and have a favorable safety profile.

Alzheimer’s disease (AD), a devastating neurodegenerative disease, is the focus of pharmacological research. One of the targets that attract the most attention for the potential therapy of AD is the serotonin 5HT6 receptor, which is the receptor situated exclusively in CNS on glutamatergic and GABAergic neurons. The neurochemical impact of this receptor supports the hypothesis about its role in cognitive, learning, and memory systems, which are of critical importance for AD. Natural products are a promising source of novel bioactive compounds with potential therapeutic potential as a 5HT6 receptor antagonist in the treatment of AD dementia. The ZINC—natural product database was in silico screened in order to find the candidate antagonists of 5-HT6 receptor against AD. A virtual screening protocol that includes both short-and long-range interactions between interacting molecules was employed. First, the EIIP/AQVN filter was applied for in silico screening of the ZINC database followed by 3D QSAR and molecular docking. Ten best candidate compounds were selected from the ZINC Natural Product database as potential 5HT6 Receptor antagonists and were proposed for further evaluation. The best candidate was evaluated by molecular dynamics simulations and free energy calculations.

In this study, we considered some pesticides as active substances within formulations for the protection of plant-based food in the Republic of Serbia in silico, because these pesticides have not often been investigated in this way previously, and in an analytical way, because there are not very many available fast, cheap, and easy methods for their determination in real agricultural samples. Seven pesticides were detected in selected agricultural products (tomatoes, cucumbers, peppers, and grapes) using the QuEChERS methodology and HPLC-DAD. Standard curves for the investigated pesticides (chlorantraniliprole, methomyl, metalaxyl, thiacloprid, acetamiprid, emamectin benzoate, and cymoxanil) show good linearity, with R² values from 0.9785 to 0.9996. The HPLC-DAD method is fast, and these pesticides can be determined in real spiked samples in less than 15 min. We further characterized the pesticides we found in food based on physicochemical properties and molecular descriptors to predict the absorption, distribution, metabolism, elimination, and toxicity (ADMET) of the compounds. We summarized the data supporting their effects on humans using various computational tools to determine their potential adverse effects. The results of our prediction study show that all of the selected pesticides considered in this study have good oral bioavailability, and those with high toxicity, therefore, could be harmful to human health. Chlorantraniliprole was shown in a molecular docking study as a good starting point for a new Alzheimer’s disease drug candidate.