Molecular modeling of cardanol-derived AChE inhibitors

Acetylcholinesterase (AChE) is the molecular target for the first-line drugs employed in treating Alzheimer's disease. A series of AChE inhibitors, designed from cardanol, a derivative of the cashew nut shell liquid, exhibits a promising inhibitory profile. By means of electronic structure calculations and principal component analysis (PCA) we pointed out the key physicochemical properties underlying the experimental data. Furthermore, by performing molecular docking into AChE's equilibrium ensemble and analyzing the distributions of energies versus root-mean-square deviation (RSMD), we noticed that the ligands assume a dual binding mode characteristic. We hope our findings contribute to the development of more potent inhibitors.