Computational Design, Molecular Docking Study and Toxicity Prediction of Some Novel Pralidoxime Derivatives as reactivators of acetyl cholinesterase enzyme

Abstract Background & Objective: oximes as Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate compounds (OPCs) intoxication. Oximes also bind to the active site of AChE, simultaneously acting as reversible inhibitors. Organophosphorus compounds (OPCs) such as soman, sarin, or VX react with acetyl cholinesterase irreversibly. In this research, a group of Pralidoxime derivatives with acetyl cholinesterase enzyme reactivator activity was subjected to a docking study, followed by a Toxicity Risk Assessment. Materials & methods: This is a descriptive-analytic study. In order to investigate the mode of the pralidoxime derivatives coupling with enzyme active site, at first the chemical structures of all compounds were designed by ChemBioDraw Ultra14.0 software. Then so as to carry out energy minimization, it transferred into a Hyperchem software. Docking study was performed by Auto Dock Vina program. Then the results were analyzed utilizing Molegro Virtual Docking software. At the final stage, the toxicity risk assessment of compounds was performed by the OSIRIS program. Results: Docking results revealed the hydrogen bond and hydrophobic interactions were involved in the drug-receptor interactions. Among the all studied compounds, the best docking results were related to No. 9 (4-methylbenzyl group- pathic compound) displayed. In fact, this compound had the most negative ΔGbind (-11.14 Kcal/mol) that indicated favorable interactions with the key amino acid residues at active site of acetyl cholinesterase. Conclusion: In conclusion, According to the results of Docking studies and the evaluation of toxicity risk, it can be concluded that combination No. 9 (4-methylbenzyl group- phatic compound) in comparison with pralidoxime reference compound might be considered as a more reactivator of the acetyl cholinesterase enzyme.