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

Aso Hameed Hasan; Faten Syahira Mohamed Yusof; Natasha Amira Kamarudin; Sankaranarayanan Murugesan; Sonam Shakya; Joazaizulfazli Jamalis

doi:10.2174/1570179420666230328121554

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

Curr Org Synth. 2023 Mar 28. doi: 10.2174/1570179420666230328121554. Online ahead of print.

Authors

Aso Hameed Hasan^{1

2}, Faten Syahira Mohamed Yusof¹, Natasha Amira Kamarudin¹, Sankaranarayanan Murugesan³, Sonam Shakya⁴, Joazaizulfazli Jamalis¹

Affiliations

¹ Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia.
² Department of Chemistry, College of Science, University of Garmian, Kalar 46021, Kurdistan Region-Iraq, Iraq.
³ Medicinal Chemistry Research Laboratory, Birla Institute of Technology & Science Pilani (BITS Pilani), Pilani Campus, Pilani-333031. Rajasthan, India.
⁴ Department of Chemistry, Faculty of Science Aligarh Muslim University, Aligarh 202002, India.

PMID: 36998126
DOI: 10.2174/1570179420666230328121554

Abstract

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.

Keywords: Anti-acetylcholinesterase; Coumarin; Molecular docking; Molecular dynamics; Psoralen; neurodegenerative disease.