Synthesis, anti-acetylcholinesterase evaluation, molecular docking and molecular dynamics simulation of novel Psoralen derivatives.

Introduction: Seven new psoralen derivatives were synthesised by carbodiimide coupling to active carboxylic acid to amide formation in mild reaction conditions.

Methods: The psoralen derivatives were produced through the condensation of seven different types of amine groups consisting of electron withdrawing groups and electron donating groups.

Results: All the synthesised compounds were obtained with moderate to high yields. Structural characterization using ATR-FTIR, 1H NMR, 13C NMR, and HRMS has confirmed their structure. Moreover, in silico evaluation of the psoralen derivatives against the AChE enzyme was performed, and acetylcholinesterase inhibitory activity of psoralen derivatives was also conducted.

Conclusion: Results from molecular docking show the potential of compound 12e as AChE inhibitors due to its highest binding energy value. It was further supported by the anti-acetylcholinesterase activity of compound 12e, which has 91.69% inhibition, comparable to galantamine (94.12%). Furthermore, 100 ns run molecular dynamics (MD) simulation was used to refine docking results.