Payame Noor University Experimental animal Biology 2322-2387 12 4 2024 04 20 Comparison of phloretin and trilobatin effect for inhibition of ‎butyrylcholinesterase activity: In vitro study and molecular ‎docking simulation Comparison of phloretin and trilobatin effect for inhibition of ‎butyrylcholinesterase activity: In vitro study and molecular ‎docking simulation 1 15 11078 10.30473/eab.2024.70624.1949 FA Mostafa Zakariazadeh Department of Biology, Payame ‎Noor University (PNU), Tehran, Iran Reza Haji Hosseini Department of Biology, Payame ‎Noor University (PNU), Tehran, Iran Reza Khodarahmi Department of Pharmacognosy and ‎Biotechnology, Faculty of Pharmacy, ‎Kermanshah University of Medical ‎Sciences, Kermanshah, Iran Somaieh Soltani Department of Medicinal Chemistry, ‎Pharmacy Faculty, Tabriz University ‎of Medical Sciences, Tabriz, 51664-‎‎14766, Iran‎ Journal Article 2024 05 08 Alzheimer's disease is the most prevalent neurodegenerative disorder affecting the central nervous system. It is crucial to prevent and treat this disease. One of the objectives in treating Alzheimer's disease is to impede the function of the butyrylcholinesterase enzyme. Phloretin and trilobatin are natural polyphenolic dihydrochalcone compounds. Trilobatin is the glycosylated derivative of phloretin. Studies have indicated the efficacy of these compounds in enhancing learning and memory as well as neuroprotective properties. The effect of these compounds on the inhibition of butyrylcholinesterase activity has been investigated in this study. The results were compared in terms of inhibitory activity and molecular mechanism of interaction for each compound. It was found that phloretin and trilobatin inhibited enzyme activity by 42% and 25%, respectively. Prediction of compounds ADMET parameters was done. Molecular docking was utilized to survey the binding mode of compounds, interaction type, and calculate the binding free energy. According to the molecular docking result, the mean binding free energy for the enzymes' interaction with phloretin and trilobatin was calculated to be -6.64(±0.35) and -5.92(±0.93) kcal/mol, respectively. The presence of a glycosylated group in the trilobatin structure increases the number of rotatable bonds, hydrophilicity, and steric hindrance. It seems that these factors reduce the inhibition activity of trilobatin against enzyme in comparison to phloretin. Based on the presented study, these compounds generally don’t have high inhibitory activity, but they can be regarded as key components in the development of novel anti-Alzheimer's drugs or as components of natural anti-Alzheimer's supplements. Alzheimer's disease is the most prevalent neurodegenerative disorder affecting the central nervous system. It is crucial to prevent and treat this disease. One of the objectives in treating Alzheimer's disease is to impede the function of the butyrylcholinesterase enzyme. Phloretin and trilobatin are natural polyphenolic dihydrochalcone compounds. Trilobatin is the glycosylated derivative of phloretin. Studies have indicated the efficacy of these compounds in enhancing learning and memory as well as neuroprotective properties. The effect of these compounds on the inhibition of butyrylcholinesterase activity has been investigated in this study. The results were compared in terms of inhibitory activity and molecular mechanism of interaction for each compound. It was found that phloretin and trilobatin inhibited enzyme activity by 42% and 25%, respectively. Prediction of compounds ADMET parameters was done. Molecular docking was utilized to survey the binding mode of compounds, interaction type, and calculate the binding free energy. According to the molecular docking result, the mean binding free energy for the enzymes' interaction with phloretin and trilobatin was calculated to be -6.64(±0.35) and -5.92(±0.93) kcal/mol, respectively. The presence of a glycosylated group in the trilobatin structure increases the number of rotatable bonds, hydrophilicity, and steric hindrance. It seems that these factors reduce the inhibition activity of trilobatin against enzyme in comparison to phloretin. Based on the presented study, these compounds generally don’t have high inhibitory activity, but they can be regarded as key components in the development of novel anti-Alzheimer's drugs or as components of natural anti-Alzheimer's supplements. https://eab.journals.pnu.ac.ir/article_11078_36d0ab1c9835c02d4497d80b17509230.pdf