20.500.12556/RUL-168084 Inhibitory potential of boscalid and abamectin towards acetylcholinesterase and butyrylcholinesterase computational and in vitro studies The growing demand for agricultural products has led to the misuse of pesticides, resulting in the use of higher concentrations of these substances. This has led to an increase in toxicity imposed on other beneficial organisms and to the bioaccumulation of toxic pesticide concentrations in the bodies of both pests and non-target organisms, as well as in their end users, including humans. In this study, the neurotoxic potential of the commonly used pesticides abamectin (an insecticide) and boscalid (a fungicide) was evaluated. Both in vitro and in silico studies showed that human butyrylcholinesterase is not a target for abamectins B1A and B1B. Boscalid showed a modest Glide score (−28.8 kJ/mol) and a considerably higher IC50 (308.8 µM) against human butyrylcholinesterase than the approved inhibitor (2-((1-(benzenesulfonyl)-1H-indol-4-yl)oxy)ethyl)(benzyl)amine (IC50 = 0.473 µM). However, due to its non-mutagenicity and low toxicity, structural analogues of boscalid might be considered as candidates for the symptomatic treatment of Alzheimer’s disease. Molecular dynamics simulations over 100 ns confirmed the stability of boscalid within the active site of butyrylcholinesterase, where it maintained key interactions with catalytic residues such as Trp82 and His438. These findings highlight its potential as a starting point for structure-based drug design strategies aimed at optimizing cholinesterase inhibitors with improved pharmacokinetic properties. According to absorption, distribution, metabolism, elimination, and toxicity studies, boscalid is orally active, which cannot be attributed to abamectins B1A and B1B. cholinesterases enzyme inhibition pesticides electron-ion interaction potential molecular docking molecular dynamics simulations true false true Angleški jezik Ni določen Članek v reviji 2025-03-28 09:35:43 2025-03-28 09:35:47 2025-10-17 12:11:27 0000-00-00 00:00:00 2025 0 0 11 str. iss. 7, art. 2865 Vol. 26 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 1422-0067 10.3390/ijms26072865 230159619 inhibitory-trobec.pdf inhibitory-trobec.pdf 1 4C073851E2BC3C0055A4D5FCF711B154 b74bc23424124652c3952f3f52ca49e3dc7c8f464452ab86498e4ab55a8003f8 40a94c8e-0bb3-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=201086 https://www.mdpi.com/1422-0067/26/7/2865 1 9d51b538-0bae-11f0-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=201082 Veterinarska fakulteta Biotehniška fakulteta 0 0 0