Synthesis of α-Naphthalene Acetic Acid Derived Bis -Schiff Bases: In Vitro Cholinesterase Inhibition, Molecular Docking, Dynamics Simulations, Kinetics, and DFT Analysis
Ayesha Bibi, Aftab Alam, Tanzeela Ahmad Shah, Burak Tüzün, Imtiaz K. Ahmad, Muhammad Ayaz, Sajjad ur Rahman, Ahmed A. Elhenawy, Syed Adnan Alı Shah, Abdul Latif, Mumtaz Ali, Manzoor Ahmad · Polycyclic aromatic compounds · 2025
This study reports the synthesis, characterization by means of spectroscopic techniques (UV, FT-IR,1H-NMR,13C-NMR and mass) and enzyme inhibitory activities (acetyl and butyryl-cholinesterase) of new bis-Schiff bases derived from α-naphthalene acetic acid. Among the synthetic library, six analogues (3a, 3b, 3 g, 3e, 3i, and 3h) showed the promising dual inhibitory activity with IC50 values from (75.53 ± 0.47 to 103.60 ± 0.91 µmol/L for acetyl cholinesterase) and (71.28 ± 0.57 to 106.60 ± 1.83 µmol/L for butyrylcholinesterase), while the remaining compounds attributed good to moderate inhibitory effects. Furthermore, Gaussian calculations were performed to examine new bis-Schiff bases at the B3LYP, HF, and M062X levels, utilizing the 6-31++g(d,p) basis set. Molecular docking calculations were performed on a number of proteins, including AChE enzyme proteins (PDB ID: 4M0E, 1OCE, and 1QTI), and BuChE enzyme proteins (PDB ID: 5NN0, 1XLU, and 6QAE). To examine the effects and responses of these drugs on human metabolism, ADME/T calculations are conducted. MD simulations highlighted 3i-4M0E complex as top candidates, with stable 3i-4M0E complexes suggesting functional relevance. These findings underscore the potential of these compounds as leads for optimizing acetylcholinesterase inhibitors in neurological disorder therapeutics.