Synthesis, biological evaluation, theoretical investigations, docking study and ADME parameters of some 1,4-bisphenylhydrazone derivatives as potent antioxidant agents and acetylcholinesterase inhibitors

Abstract

Five 1,4-bisphenylhydrazone derivatives (15) were successfully synthesized and evaluated for their antioxidant and acetylcholinesterase inhibitory activities. The antioxidant activity has been carried out using DPPH, ABTS, CUPRAC and superoxide radical scavenging methods. All the compounds showed a very good antioxidant activity compared to that of the standards used. Compound 1 was found to be the best antioxidant agent with IC50 values lower or comparable to that of the standards. The acetylcholinesterase inhibitory activity has been evaluated using a modified Ellman’s assay. The obtained results indicate that compound 2 is the best acetylcholinesterase inhibitor with a low IC50 value comparable to that of the galantamine. In addition, DFT calculations have been performed to determine in which mechanism the synthesized hydrazones follow to scavenge free radicals. Molecular docking study was performed for compound 2, and its interaction modes with the enzyme acetylcholinesterase were determined. As a result, a strong interaction between this compound and the active site of AChE enzyme was revealed. Finally, ADME properties of the synthesized compounds were also studied and showed good drug-like properties.

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Acknowledgements

We would like to thank MESRS (Ministère de l’Enseignement Supérieur et de la Recherche Scientifique, Algeria) and DGRST (Direction Générale de la Recherche Scientifique et Technologique, Algeria) for financial support, as well as the HPC resources of UCI-UFMC (Unité de Calcul Intesif) of the university Fréres Mentouri Constantine 1 for the computational resources used. We also thank Dr. Bensouici Chawki (Centre de recherche en Biotechnologie CRBt, Constantine, Algeria) for his help in the biological evaluation.

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Amine Khodja, I., Boulebd, H. Synthesis, biological evaluation, theoretical investigations, docking study and ADME parameters of some 1,4-bisphenylhydrazone derivatives as potent antioxidant agents and acetylcholinesterase inhibitors. Mol Divers 25, 279–290 (2021). https://doi.org/10.1007/s11030-020-10064-8

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Keywords

  • Hydrazone
  • Acetylcholinesterase
  • Antioxidant activity
  • Docking study
  • DFT calculations
  • ADME parameters