Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases

Rahim F 1 , Ullah H 2 , Taha M 3 , Wadood A 4 , Javed MT 2 , Rehman W 2 Show all authors , Nawaz M 2 , Ashraf M 5 , Ali M 6 , Sajid M 7 , Ali F 2 , Khan MN 2 , Khan KM 8

Affiliations 

  • 1 Department of Chemistry, Hazara University, Mansehra 21300, Pakistan. Electronic address: fazalstar@gmail.com
  • 2 Department of Chemistry, Hazara University, Mansehra 21300, Pakistan
  • 3 Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science, UiTM, 40450 Shah Alam, Selangor, Malaysia
  • 4 Department of Biohemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
  • 5 Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
  • 6 Center for Advanced Drug Research, COMSATS Institute of Information Technology, University Road, Abbottabad 22060, KPK, Pakistan
  • 7 Department of Biochemistry, Hazara University, Mansehra 21300, Pakistan
  • 8 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Bioorg Chem, 2016 10;68:30-40.
PMID: 27441832 DOI: 10.1016/j.bioorg.2016.07.005

Abstract

To discover multifunctional agents for the treatment of Alzheimer's disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC50 values 4.12±0.01, 8.12±0.01 and 8.41±0.06μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC50=0.85±0.0001μM). Three compounds 13, 24 and 3 having IC50 values 6.51±0.01, 9.22±0.07 and 37.82±0.14μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC50=0.04±0.0001μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications