EVALUATION OF THE INTERACTION OF AGROCHEMICALS WITH ACETYLCHOLINESTERASE: AN IN SILICO ANALYSIS OF TOXICITY CLASSES

Resumo

INTRODUCTION: The exposure to agricultural pesticides is a widely debated topic due to their negative impacts on human health and the environment. Acetylcholinesterase (AChE) is one of the main toxicological targets of these substances and is responsible for regulating acetylcholine levels in the nervous system, making it a relevant focus for studies involving such compounds. OBJECTIVE: This study investigates the interactions between pesticides from the organophosphate and carbamate classes with AChE. MATERIAL AND METHODS: The ligand structures were obtained from the PubChem database (NCBI), while the crystallographic structure of acetylcholinesterase (PDB: 5FPQ) was retrieved from the Protein Data Bank (PDB) and underwent preprocessing, during which solvent molecules, ions, and non-essential ligands were removed. RESULTS: Benfuracarb exhibited the highest binding affinity (-7.22 kcal/mol), followed by Chlorpyrifos (-6.66 kcal/mol) and Carbofuran (-6.51 kcal/mol). Malathion (-5.22 kcal/mol) and Acephate (-4.55 kcal/mol) showed lower affinities, while Sarin, used as a comparison parameter, recorded the lowest affinity, with -3.78 kcal/mol. Benfuracarb had the lowest Ki value (5.10 µM), followed by Chlorpyrifos (13.13 µM) and Carbofuran (16.91 µM). Diazinon (9.03 µM) and Fenobucarb (Class II, 29.51 µM) showed intermediate values, while Malathion (0.15 mM) and Acephate (0.46 mM) had higher values. Methomyl (Class I, 0.42 mM) performed below expectations for its class, whereas Sarin, with a Ki of 1.70 mM, was the least effective compound. Regarding ligand efficiency, Sarin proved to be the most efficient, with the most negative value (-0.47). Methomyl (-0.46) and Acephate (-0.45) also demonstrated high efficiency. Carbofuran (-0.41), Fenobucarb (-0.41), Chlorpyrifos (-0.37), and Diazinon (-0.34) showed intermediate values. Malathion (-0.27) and Benfuracarb (-0.26) had the lowest efficiencies. CONCLUSION: Class I compounds, such as Benfuracarb and Carbofuran, showed greater interaction with AChE, highlighting their high toxicity. However, Class II compounds, such as Chlorpyrifos and Diazinon, presented competitive performance, indicating that toxicity is not exclusively related to classification. The Ki values and ligand efficiencies suggest that the potential toxicity of carbamates is higher than that of organophosphates.