Synthesis of α-Naphthalene Acetic Acid Derived Bis-Schiff Bases: In Vitro Cholinesterase Inhibition, Molecular Docking, Dynamics Simulations, Kinetics, and DFT Analysis

Bibi A., Alam A., Shah T. A., TÜZÜN B., Ahmad I., Ayaz M., ...Daha Fazla

Polycyclic Aromatic Compounds, 2025 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1080/10406638.2025.2551791
  • Dergi Adı: Polycyclic Aromatic Compounds
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Applied Science & Technology Source, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Computer & Applied Sciences, Food Science & Technology Abstracts, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Anahtar Kelimeler: acetylcholinesterase, Bis-Schiff bases/azines, butyrylcholinesterase, density functional theory, molecular docking and dynamics simulations, structure activity relationship
  • Sivas Cumhuriyet Üniversitesi Adresli: Evet

Özet

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.