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

Fazal Rahim; Muhammad Tariq Javed; Hayat Ullah; Abdul Wadood; Muhammad Taha; Muhammad Ashraf; Qurat-ul-Ain; Muhammad Anas Khan; Fahad Khan; Salma Mirza; Khalid M Khan

doi:10.1016/j.bioorg.2015.08.002

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

Bioorg Chem. 2015 Oct:62:106-16. doi: 10.1016/j.bioorg.2015.08.002. Epub 2015 Aug 19.

Authors

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.

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.

Keywords: Acetylcholinesterase inhibition; Alzheimer’s disease; Butyrylcholinesterase Inhibition; Molecular docking; Synthesis; Thiazole.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease*
Butyrylcholinesterase
Catalytic Domain
Cholinesterase Inhibitors / pharmacology*
Molecular Docking Simulation
Thiazoles / pharmacology*

Substances

Cholinesterase Inhibitors
Thiazoles
Butyrylcholinesterase