Computer-aided drug design approach for alkaloids isolated from Miers as potential acetylcholinesterase inhibitors.

Considering the medicinal importance of alkaloids from Miers, five major compounds (stepharine, stepharanine, stepholidine, palmatine and tetrahydropalmatine) from the plant were analyzed for their acetylcholinesterase activity using molecular docking, molecular dynamics simulations and pharmacokinetics. As acetylcholinesterase has been significantly studied for their role in Alzheimer's disease, the enzyme from (PDB ID: 1QTI) was taken as a receptor protein. AutoDock Vina was used to study the docking affinities during the initial screening of compounds where, stepharine showed promising binding energy (-10.3 kcal/mol) forming crucial interactions with active site residues (His 440, Tyr 121, and Trp 84). Molecular dynamics simulations were performed for 200 ns to analyze the stability of the docked complex. The study of trajectories obtained after simulation showed stepharine with a strong binding affinity and stability with AChE. Moreover, drug likeness and ADMET analysis conducted via Swiss ADME and pKCSM affirmed stepharine's favorable pharmacological properties. Overall, this research highlights stepharine as a potent acetylcholinesterase inhibitor which could be further developed as potential drug against Alzheimer's disease.