Abstract

Mahalakshmi C. S. Parepalli ^{1, 2} and Rajitha Galla^2*

The successful treatment strategy for Alzheimer's disease focuses on inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to enhance cholinergic activity. This study aimed to design fifteen 9H-(fluorenyl)methyl lysine carbamate derivatives (4a-o) as potential BChE inhibitors and perform molecular docking studies to identify their binding sites and evaluate their binding mechanisms on the BChE protein by Glide software. The results revealed that the most potent compounds were 4a, 4c, and 4j, with docking scores of -10.53, -10.57, and -10.85 kcal/mol, respectively indicating strong binding affinities with the BChE enzyme, suggesting as potential inhibitors. Notably, compound 4j exhibited complete oral absorption, high permeability in MDCK cells, and good skin permeability. Its surface area components were within acceptable ranges. Thus, compound 4j is proposed as a promising candidate for experimental evaluation as a BChE inhibitor.

Alzheimer Disease; Acetylcholinesterase; ADME studies; Butyrylcholinesterase; Molecular Docking

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