Molecular docking and dynamics simulation approach of leaf extract derived compounds as potential cholinesterase inhibitors.

The tea plant () belongs to the family Theaceae and contains many phytochemicals that are effective against various diseases, including neurodegenerative disorders. In this study, we aimed to characterize the phytochemicals present in the methanolic and n-hexane leaf extracts of using GC-MS, FTIR, and UV-visible analysis. We detected a total of 19 compounds of different chemical classes. We also performed molecular docking studies using the GC-MS detected phytochemicals, targeting acetylcholinesterase (AChE, PBD ID: 4BDT) and butyrylcholinesterase (BChE, PDB ID: 6QAB), which are responsible for the breakdown of the neurotransmitter acetylcholine (ACh). This breakdown leads to dementia and cognitive decline in Alzheimer's patients. The compounds Ergosta-7,22-dien-3-ol, (3.beta.,5.alpha.,22E)- and Benzene, 1,3-bis(1,1-dimethylethyl) showed better binding affinity against AChE, while dl-.alpha.-Tocopherol and Ergosta-7,22-dien-3-ol, (3.beta.,5.alpha.,22E)- showed better binding affinity against BChE. We determined the stability and rigidity of these best docked complexes through molecular dynamics simulation for a period of 100 ns. All complexes showed stability in terms of SASA, Rg, and hydrogen bonds, but some variations were found in the RMSD values. Our ADMET analysis revealed that all lead compounds are non-toxic. Therefore, these compounds could be potential inhibitors of AChE and BChE.