Unlocking Therapeutic Potential of Alkaloids Inhibiting Acetylcholine Esterase: A Comparative Molecular Docking and MD Simulation Analysis with Known Drugs of Galantamine and Physostigmine

Abstract

Alzheimer's disease is characterized by the degeneration of neurons in the central nervous system. Patients with Alzheimer's disease experience cognitive problems like memory loss and reasoning impairments, which are brought on by a decrease in neuronal activity and a drop in the levels of neurotransmitters in the intersynapse. The Fritillaria genus, which comprises a variety of culinary and medicinal plants from the Liliaceae family, is extensively cultivated and has a long history in Xinjiang, China. been used in Chinese traditional medicine. The primary component of this plant is alkaloids, of which there are over 40 known varieties. . Most of Alkaloids are the main important compounds used in treatment of different disease, so it will have an effective role in the treatment of Alzheimer’s as well. Insilico approach including molecular docking, ADME, Toxicity, bioactivity check and Molecular Dynamic Simulation was applied for evaluation of their potential to treat Alzheimer’s disease.Computationalfindings of the current study reveals thatHuperzine A (-9.6kcal/mol), Berberine (-10.6kcal/mol) andPiperine (-9.6kcal/mol) may act as a drug candidate as they follow all five guidelines of Lipinski,high binding affinities and having equal or less than 3Å of RMSF value in average, which indicates the stability of complexes.