Synthesis, molecular docking, acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease

Rahim F 1 , Javed MT 2 , Ullah H 2 , Wadood A 3 , Taha M 4 , Ashraf M 5 Show all authors , Qurat-ul-Ain 5 , Khan MA 6 , Khan F 2 , Mirza S 7 , Khan KM 7

Affiliations 

  • 1 Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan. Electronic address: [email protected]
  • 2 Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan
  • 3 Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan
  • 4 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
  • 5 Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan
  • 6 National Centre of Excellence in Physical Chemistry, University of Peshawar, KPK, Pakistan
  • 7 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
Bioorg Chem, 2015 Oct;62:106-16.
PMID: 26318401 DOI: 10.1016/j.bioorg.2015.08.002

Abstract

A series of thirty (30) thiazole analogs were prepared, characterized by (1)H NMR, (13)C NMR and EI-MS and evaluated for Acetylcholinesterase and butyrylcholinesterase inhibitory potential. All analogs exhibited varied butyrylcholinesterase inhibitory activity with IC50 value ranging between 1.59±0.01 and 389.25±1.75μM when compared with the standard eserine (IC50, 0.85±0.0001μM). Analogs 15, 7, 12, 9, 14, 1, 30 with IC50 values 1.59±0.01, 1.77±0.01, 6.21±0.01, 7.56±0.01, 8.46±0.01, 14.81±0.32 and 16.54±0.21μM respectively showed excellent inhibitory potential. Seven analogs 15, 20, 19, 24, 28, 30 and 25 exhibited good acetylcholinesterase inhibitory potential with IC50 values 21.3±0.50, 35.3±0.64, 36.6±0.70, 44.81±0.81, 46.36±0.84, 48.2±0.06 and 48.72±0.91μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking.

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

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