Design and synthesis of novel carbamate derivatives as cholinesterase inhibitors for the treatment of Alzheimer's disease: bioassay and molecular dynamics

• Novel carbamate derivatives as cholinesterase inhibitors were synthesized. • Compounds exhibit notable cholinesterase inhibitory and neuroprotective activities. • Compounds 3c and 3a have acceptable predicted ADME and physicochemical properties. • 3a and 3c computerized models show good ligand-protein interactions. • QSAR models suggest cholinesterase inhibitor candidates for Alzheimer’s treatment. The crucial role of acetylcholinesterase (AChE) and butyryl cholinesterase (BuChE) enzymes in neural transmission and brain cell health has positioned them as key elements in understanding Alzheimer's disease (AD) progression. Consequently, researchers developed and evaluated 40 new carbamate compounds ( 3a-t and 4a-t ) as enzyme inhibitors, based on the framework of natural substrates and established enzyme blockers. Additional tests examined cell toxicity and protective effects in H 2 O 2 -damaged SHSY-5Y cells, followed by ADMET analysis. Potential molecule-enzyme interactions were studied through molecular docking and dynamics studies. The Ellman enzyme inhibition assay showed promising IC 50 values for 3c and 3a against AChE (1.4 µM) and BuAChE (0.2 µM) respectively. Minimal cell toxicity combined with effective neuroprotection and suitable ADMET characteristics clarified the compounds' safety and drug-like properties. A QSAR model was also developed for inhibitors.