Anticholinesterase activities of novel indole-based hydrazide-hydrazone derivatives: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction

Coşar E. D., DİNCEL E. D., Demiray S., Sucularlı E., Tüccaroğlu E., ÖZSOY N., ...More

JOURNAL OF MOLECULAR STRUCTURE, vol.1247, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1247
  • Publication Date: 2022
  • Doi Number: 10.1016/j.molstruc.2021.131398
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Keywords: Acetylcholinesterase, Butyrylcholinesterase, Hydrazide-hydrazones, Synthesis, Computer-aided drug design, ADME properties, ALZHEIMERS-DISEASE, POTENTIAL INHIBITORS, ANTICANCER ACTIVITY, ACCURATE DOCKING, ACETYLCHOLINESTERASE, GLIDE, TRIAZOLE, PROTEIN, HYBRIDS, AGENTS
  • Istanbul University Affiliated: Yes


A series of novel indole-based hydrazide-hydrazone derivatives were synthesized and evaluated for their AChE and BuChE inhibitory activities. The structural elucidations of the novel compounds (2a-k ) were performed by IR, H-1-NMR, C-13-NMR, mass, and elemental analysis. The inhibitory potential of the novel compounds on AChE (from electric eel) and BuChE (from equine serum) enzymes were carried out using in vitro modified Ellman's spectrophotometric method. Compounds 2f and 2d displayed the highest AChE inhibitory activity. Furthermore, 2d displayed the best BuChE inhibitory activity which was comparable with Galantamine. In addition to the in vitro analysis, docking studies targeting AChE (PDB ID: 1EVE) and BuChE (PDB ID: 4BDS) were performed to understand the possible interactions of these compounds with the enzymes. Structure-activity relationships, as well as in silico ADME studies, were performed and a relationship between biological, electronic, and physicochemical qualifications of the title compounds was determined. (C) 2021 Elsevier B.V. All rights reserved.