Synthesis,molecular docking,acetylcholinesterase and butyrylcholinesterase inhibitory potential of thiazole analogs as new inhibitors for Alzheimer disease |
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| Institution: | 1. Department of Chemistry, Hazara University, Mansehra, Khyber Pakhtunkhwa, Pakistan;2. Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan;3. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia;4. 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;1. Department of Biotechnology, National Institute of Technology, Raipur, Chhattisgarh, India;2. Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong, India;1. Department of Chemistry, Hazara University, Mansehra 21120, Pakistan;2. Department of Pharmacy, University of Malakand, Chakdara, 18000 Dir (L), Pakistan;3. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;1. Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), University of Dammam, Dammam 31441, Saudi Arabia;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;4. Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Malaysia;6. Department of Pharmacology, Faculty of Medicine, CUCMS, Cyberjaya, Selangor 63000, Malaysia;7. H. E. J. RIC, ICCBS, University of Karachi, Karachi 75270, Pakistan;1. Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria;2. Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 9, 1113 Sofia, Bulgaria;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia;2. Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;3. Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia;4. Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah 51452, Saudi Arabia;5. Department of Pharmacology, Faculty of Medicine, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia;6. Department of Pharmaceutics, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia;1. Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan;2. Department of Chemistry, Govt. College Women University, Sialkot 51300, Pakistan;3. Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan;4. Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad, Pakistan;5. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan |
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| Abstract: | A series of thirty (30) thiazole analogs were prepared, characterized by 1H NMR, 13C 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 ± 1.75 μM when compared with the standard eserine (IC50, 0.85 ± 0.0001 μM). 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 ± 0.21 μM 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 ± 0.91 μM respectively. All other analogs also exhibited well to moderate enzyme inhibition. The binding mode of these compounds was confirmed through molecular docking. |
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| Keywords: | Alzheimer’s disease Acetylcholinesterase inhibition Butyrylcholinesterase Inhibition Thiazole Synthesis Molecular docking |
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