Synthesis, Anti-acetylcholinesterase Evaluation, Molecular Docking and Molecular Dynamics Simulation of Novel Psoralen Derivatives

Abstract

Introduction: Seven new psoralen derivatives were synthesised by carbodiimide cou-pling 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 per-formed, and acetylcholinesterase inhibitory activity of psoralen derivatives was also conducted. Conclusion: Results from molecular docking show the potential of compound 12e as AChE inhib-itors 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 galan-tamine (94.12%). Furthermore, 100 ns run molecular dynamics (MD) simulation was used to re-fine docking results.