Inhibitory potential of boscalid and abamectin towards acetylcholinesterase and butyrylcholinesterase : computational and in vitro studies

Arsić, Biljana (author), Petrović, Stefan (author), Ilić, Budimir S. (author), Vrecl, Milka (author), Trobec, Tomaž (author), Sepčić, Kristina (author), Frangež, Robert (author), Glisić, Sanja (author), Milićević, Jelena S. (author)

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.

• Language: English
• Keywords: cholinesterases, enzyme inhibition, pesticides, electron-ion interaction potential, molecular docking, molecular dynamics simulations
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: VF - Veterinary Faculty; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 11 str.
• Numbering: Vol. 26, iss. 7, art. 2865
• PID: 20.500.12556/RUL-168084
• UDC: 616-092
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms26072865
• COBISS.SI-ID: 230159619
• Publication date in RUL: 28.03.2025

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

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• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.