Supplementary file 1_Virtual screening of phytochemicals against multiple protein targets of Alzheimer’s disease.docx

Docking results showed potential strong binding of 96 compounds at multiple key targets, and molecular dynamics simulations of the representative compounds Lactucopicrin, Oleanolic acid and Rutecarpine in complex with AChE and GSK3β demonstrated stable protein-ligand complexes, comparable to the known AChE-ligand, Donepezil, and the GSK3β-ligand, QQA. Post-docking filters based on multitarget and heavy atoms count narrowed the selection to 36 compounds.

These 36 compounds were classified into families of Alkaloids (Rutecarpine, Sanguinarine, Strychnine), Steroidal alkaloids (Tomatidine, Cyclopamine, Jervine, Verticine, Verticinone), Steroidal sapogenins (Diosgenin, Hecogenin, Yamogenin, Tigogenin, Smilagenin, Sarsasapogenin, Neogitogenin, Ruscogenin), Triterpenoids/sterols (alpha-Spinasterin, Fucosterol, Stigmasterol, Beta-Sitosterol, gamma-Sitosterol, Isofucosterol, Germanicol, Lupeol, Beta-Amyrin, alpha-Amyrin, Taraxerol, Friedelin, Tetrahymanol, Tingenone, Parkeol, Methylenecycloartanol, Ursolic Acid, Oleanolic Acid, Obacunone), and Sesquiterpene (Lactucopicrin).

Multiple compounds were supported by the literature, which shows that they can inhibit amyloid aggregation, tau phosphorylation, neuroinflammation, and cholinergic dysfunction, thus lending credibility to our claims. Collectively, our findings suggest that several of the identified multitarget phytochemicals are promising candidates for further experimental validation in AD therapy.</p>