In Silico Evaluation of Daechualkaloid A Maltoxazine as a Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease: A Docking, DFT, and SwissADME-Based Study

Abstract Daechualkaloid A Maltoxazine, a naturally occurring alkaloid, is a known medicinal plant used in Asia traditional medicine for different diseases. In this study, we performed density functional theory (DFT) calculations using the Gaussian 09W software package at the level of B3LYP using 6-311G** basis set and molecular docking for determining the inhibitory potential of Daechualkaloid A Maltoxazine against Alzheimer’s disease targets. The HOMO and LUMO calculated values came out as -5.622 and -1.415 respectively with the energy gap of 4.207, which shows that the compound has stable configuration. The molecular docking against acetylcholinesterase (AChE, PDB ID: 1EVE) showed a docking score of -8.6 kcal/mol. The results also showed that GLY119 and SER200 form a hydrogen bond with the ligand. Furthermore, the SwissADME study revealed good physicochemical properties of the compound, having a molecular mass of 179.22 g/mol. The compound also exhibited optimal lipophilicity, water solubility, and gastrointestinal absorption properties. Similarly, it can pass through blood brain barrier and adhere almost to all druglikeness filters including the Lipinski rule of five. These findings suggest that Daechualkaloid A Maltoxazine could be a potential candidate for further experimental validation in Alzheimer’s disease drug development and other related diseases