Synthesis, molecular docking and biochemical analysis of aminoalkylated naphthalene-based chalcones as acetylcholinesterase inhibitors

Abstract

Twelve novel chalcones were synthesized using 2-alkyloxy-naphthaldehydes and Mannich bases of 4-hydroxyacetophenone. The chalcones were characterized using FTIR, 1D and 2D NMR and HRMS spectroscopy. Comparative docking analysis was carried out to screen their affinity towards the AChE enzyme (PDB 1EVE). All chalcones showed lower binding energy (−13.06 to −10.43 kcal/mol) against AChE better than donepezil (−10.52 kcal/mol). All chalcones were potent inhibitors towards AChE, with IC50 values ranging between 0.11 and 5.34 nM better than donepezil (IC50 33.4 nM) and selectivity indexes (0.66–23.83), despite the fact that chalcones 10 and 13 were inactive. The structure activity relationship indicated that introducing diethyl amine in ring A of the chalcone skeleton and the propargyl moiety at ring B was affirmed to be a prospective drug against AChE. The multifunctional properties of chalcone 15 were all advantages that demonstrate an excellent candidate for the development of an effective drug against AChE.

Keywords

• acetylcholinesterase
• chalcone
• dpph
• docking
• structure–activity relationship