Utilizing FEL, PCA, DCCM, MM-GBSA and SIE methods, we systematically investigated the influence of phosphorylation and ligand binding on the conformational dynamics of BACE1 through Gaussian accelerated molecular dynamics (GaMD) trajectories.
Drug-like molecules designed by fragment growing strategy on isocytosine and acyl guanidine warheads as BACE1 inhibition. In vivo characterization of top-active benzimidazoles (16a, 16k) showed Aβ/oxidation stress reduction and brain/liver safety.
This review highlights the potential of multi-target-directed strategies that address amyloid-β aggregation, metal ion dyshomeostasis, and enzyme dysfunction, offering a comprehensive and effective approach to treating Alzheimer's disease.
Proaporphine alkaloids—cissamaline, cissamanine, and cissamdine—show promise against AD, with in silico studies highlighting their potential as new therapeutics.
New phosphazine and triazole derivatives were synthesized and evaluated as potential anti-Alzheimer's agents. The compounds modulate ROS/JNK and Wnt/β-catenin pathways, showing promising neuroprotective activities.