The Relationship Between AChE and BChE Enzymes and Alzheimer’s Disease: ADME, Molecular Docking, and DFT Studies of Schiff Base-Substituted Phenylpyrimidine

Authors : Kenan Gören, Mehmet Bağlan, Veysel Tahiroğlu, Ümit Yıldıko

Pages : 1-15

Doi:10.18466/cbayarfbe.1538029

View : 156 | Download : 143

Publication Date : 2025-12-29

Article Type : Research Paper

Abstract :The theoretical molecular structure of Ethyl 2-(2-benzylidenehydrazinyl)-4-methyl-6-phenylpyrimidine-5-carboxylate (DHPM), a pyrimidine derivative containing the Schiff base structure, was investigated using the Gaussian 09 software program. The chemical structure and chemical reactivity of the compound were calculated using Density Functional Theory (DFT). Quantum chemical calculations were performed using DFT(B3LYP/6-311G(d,p)) and DFT(B3PW91/LANL2DZ) methods and basis sets. Using these two methods and basis sets, molecular electrostatic potential (MEP) maps of the DHPM compound were drawn. Charge transfer properties of DHPM compound were analyzed using HOMO and LUMO level energy analysis. The stability of molecules as a consequence of charge delocalization and hyperconjugative interaction was studied using NBO analysis. In this study, the relationship between Alzheimer\\\'s disease and Acetylcholinesterase (AChE) (PDB:6WUY) and Butyrylcholinesterase (BChE) (PDB: 6SAM) enzymes was evaluated by molecular docking. The molecular docking scores of in molecular docking analysis were found to be -7.76 (PDB ID: 6WUY) and -7.98 (PDB ID: 6SAM) kcal. Finally in the study, ADME analysis was performed to evaluate DHPM compound as a drug according to Lipinski\\\'s rules. As a result of the ADME analysis, we think that DHPM compound will be evaluated as a drug candidate since it complies with Lipinski\\\'s rules.
Keywords : DFT, Molecular Docking, ADME, NBO, Alzheimer, 2-(2-benzylidenehydrazinyl)-4-methyl-6-phenylpyrimidine-5-carboxylate.

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