Computational design and evaluation of tacrine-based carbamate derivatives as acetylcholinesterase inhibitors.

> 0.93) show the influence of steric and hydrogen bond donor effects on activity. Then, four new derivatives were proposed and tested. The ADMET analysis revealed good pharmacokinetic properties and low predicted toxicity. The DFT calculations characterized the electronic properties of the designed derivatives, and the docking results showed stronger contacts within the active sites of TcAChE (2CKM) and hAChE (4EY7). The selected complexes with both AChE structures were stable in the molecular dynamics simulations for 200 ns. The binding energies and stable conformational behavior of the selected complexes were further confirmed by MM-GBSA, PCA, FEL and DCCM analyses. Overall, the results indicate that the designed derivatives could be promising candidates for AChE inhibition in Alzheimer's disease.