Akademik Veri Yönetim Sistemi
LETTERS IN DRUG DESIGN & DISCOVERY, cilt.20, sa.12, ss.1911-1921, 2023 (SCI-Expanded)
Background Torpedo californica acetylcholinesterase (TcAChE) is an important drug development target for Alzheimer's disease (AD) therapeutics. The current in silico study aims to recognise indene methylene-derived compounds acting against TcAChE to gain insight into the molecular interactions. Objective The current study focused on identifying novel inhibitors for Torpedo californica acetylcholinesterase (TcAChE) by virtual screening, molecular docking, drug-likeness, molecular simulation, and DFT profile for anti-Alzheimer's activity. Methods Molecular docking, ADMET screening, molecular simulation, and DFT were performed for drug development having anti-Alzheimer's activity related to Torpedo californica acetylcholinesterase (TcAChE). Results On the AutoDock Vina algorithms, ligands SD-24 [-12.6, -13.1 kcal/mol], SD-30 [-12.5, -12.6 kcal/mol], SD-42 [-11.8, -12.5kcal/mol] showed promising docking and confirmatory redocking scores compared to Donepezil [-8, -10.9 kcal/mol], followed by ADMET screening. The best three complexes were subjected to molecular dynamics simulations (MDSs) over 30 ns to understand the TcAChE dynamics and behavior in a complex with the ligand. MEP and NBO analysis was performed for the DFT/B3LYP theory and 6-311G [d,p] base set and Gaussian 09 package program. For MDSs, the root means square (RMSD) parameter remained stable for 30 ns at 0.25 nm. The ligand-AChE complex formed 2 to 4 satisfactory intermolecular H bonds, which substantiated the stability of the three compounds in the protein binding cluster as potent binders. The LUMO (owest unoccupied molecular orbital)-HOMO (highest occupied molecular orbital) energy gap of the SD24, SD30, and SD42 compounds was 4.0943, 4.2489, and 4.2489 eV, respectively, and stability was ordered as SD24>SD30=SD42. Conclusion The outcome of in silico studies suggests that SD24, SD30, and SD42 compounds have promising drug-likeness, simulation, and DFT profiles for anti-Alzheimer's activity. However, in vitro and in vivo studies are required to confirm their biological activities.