Evaluating Blood-Brain Barrier Permeability, Cytotoxicity, and Activity of Potential Acetylcholinesterase Inhibitors: In Vitro and In Silico Study.

ABSTRACT: Acetylcholinesterase inhibitors (AChEIs) remain the first-line treatment for Alzheimer's disease. However, these drugs are largely symptomatic and often associated with adverse effects. This study aimed to evaluate novel pharmacophores for their in vitro AChEI activity, blood-brain barrier (BBB) permeability, and cytotoxic potential, hypothesizing that a combination of AChEIs could enhance symptom management while minimizing toxicity. A library of 1453 synthetic pharmacophores was assessed using in vitro and in silico methods to determine their feasibility as an inhibitor of the AChE enzyme. An in-house miniaturized Ellman's assay determined acellular AChEI activities, while pharmacokinetic properties were evaluated using the SwissADME web tool. The combinational effects of in silico BBB-p

SUBMITTER: Maboko LM 

PROVIDER: S-EPMC11841676 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature