Acetylcholinesterase (AChE) enzymes play an essential role in the development of Alzheimer’s disease (AD). Its excessive activity causes several neuronal problems, particularly psychopathies and neuronal cell death. A bioactive pose on the hAChE B site of the human acetylcholinesterase (hAChE) enzyme employed in this investigation, which was obtained from the Protein Data Bank (PDB ID 4EY6), allowed for the prediction of the binding affinity and free binding energy between the protein and the ligand. Virtual screening was performed to obtain structures similar to Galantamine (GNT) with potential hAChE activity. The top 200 hit compounds were prioritized through the use of filters in ZincPharmer, with special features related to the pharmacophore. Critical analyses were carried out, such as hierarchical clustering analysis (HCA), ADME/Tox predictions, molecular docking, molecular simulation studies, synthetic accessibility (SA), lipophilicity, water solubility, and hot spots to confirm the stable binding of the two promising molecules (ZINC16951574-LMQC2, and ZINC08342556-LMQC5). The metabolism prediction, with metabolites M3-2, which is formed by Glutathionation reaction (Phase II), M1-2, and M2-2 formed from the reaction of S-oxidation and Aliphatic hydroxylation (Phase I), were both reactive but with no side effects. Theoretical synthetic routes and prediction of synthetic accessibility for the most promising compounds are also proposed. In conclusion, this study shows that in silico modeling can be used to create new drug candidate inhibitors for hAChE. The compounds ZINC16951574-LMQC2, and ZINC08342556-LMQC5 are particularly promising for oral administration because they have a favorable drug-likeness profile, excellent lipid solubility, high bioavailability, and adequate pharmacokinetics.

When an epidemic started in the Chinese city of Wuhan in December 2019, coronavirus was identified as the cause. Infection by the virus occurs through the interaction of viral S protein with the hosts’ angiotensin-converting enzyme 2. By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation. The FTMap server and the Molegro software were used to determine the active site of the Spike-ACE2 protein’s crystal structure. Virtual screening was performed using a pharmacophore model obtained from antiparasitic drugs, obtaining 2000 molecules from molport^®. The ADME/Tox profiles were used to identify the most promising compounds with desirable drug characteristics. The binding affinity investigation was then conducted with selected candidates. A molecular docking study showed five structures with better binding affinity than hydroxychloroquine. Ligand_003 showed a binding affinity of −8.645 kcal·mol⁻¹, which was considered an optimal value for the study. The values presented by ligand_033, ligand_013, ligand_044, and ligand_080 meet the profile of novel drugs. To choose compounds with favorable potential for synthesis, synthetic accessibility studies and similarity analyses were carried out. Molecular dynamics and theoretical IC₅₀ values (ranging from 0.459 to 2.371 µM) demonstrate that these candidates are promising for further tests. Chemical descriptors showed that the candidates had strong molecule stability. Theoretical analyses here show that these molecules have potential as SARS-CoV-2 antivirals and therefore warrant further investigation.

This study investigated the neuroprotective potential of Xanthoceras sorbifolium Bunge (XSB) seed oil through fatty acid profiling, antioxidant assays, and in silico targeting of FABP7. Among the solvent-to-solid ratios tested, 1:20 (w/v) gave the highest oil yield (72.91%) and the strongest ABTS, DPPH, and FRAP activities. GC-MS identified 17 fatty acids from the 1:20 (w/v) oil extract, with linoleic acid (38.93%) and oleic acid (31.3%) as the major constituents. Following GC-MS fatty acid profiling, lipid structural characterization was performed using ¹H NMR and FT-IR. ADME/T prediction and BOILED-EGG analysis suggested favorable pharmacokinetic properties and BBB permeability for the selected fatty acids. Molecular docking and simulation revealed strong and stable interactions of five compounds with FABP7: nervonic acid (−6.1 kcal/mol), erucic acid (−6.002 kcal/mol), eicosadienoic acid (−6.08 kcal/mol), oleic acid (−6.03 kcal/mol), and linoleic acid (−6.00 kcal/mol), outperforming the native ligand, oleic acid (−5.8 kcal/mol). These findings indicate that XSB seed oil contains bioactive lipids with promising FABP7-targeted neuroprotective potential and warrant further investigation as therapeutic leads for neurodegenerative diseases.