Donepezil-based rational design of N -substituted quinazolinthioacetamide candidates as potential acetylcholine esterase inhibitors for the treatment of Alzheimer's disease: in vitro and in vivo studies
Ahmed Ali Al-Karmalawy, Ahmed F. Mohamed, Heba Nasr Shalaby, Ayman Abo Elmaaty, Riham A. El‐Shiekh, Mohamed A. Zeidan, Radwan A. Alnajjar, Abdullah Yahya Abdullah Alzahrani, Mohammed H. AL Mughram, Moataz Ahmed Shaldam, Haytham O. Tawfik · RSC Medicinal Chemistry · 2025
< 0.0001) compared to STZ mice. Such effects were similar to those of donepezil which reduced all 3 parameters by 57.53%, 58.5%, and 66.78%, respectively, compared to STZ mice. Furthermore, molecular docking studies showed that the superimposition view clarified the similar binding mode of both 3e and the co-crystallized donepezil at the AChE binding pocket. Moreover, the docked complexes (3e-AChE and 3e-BuChE) were further subject to molecular dynamics simulations for 100 ns. In addition, eligible pharmacokinetic profiles as well as feasible BBB penetration were anticipated for compound 3e using ADME and BBB permeation prediction studies. Accordingly, the synthesized compounds, in particular compound 3e, can be treated as promising lead compounds for AD treatment with future further optimization.