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Novel Tacrine-Coumarin Hybrids Linked to 1,2,3-Triazole As Anti-Alzheimer's Compounds: In Vitro and in Vivo Biological Evaluation and Docking Study Publisher Pubmed



Najafi Z1, 2 ; Mahdavi M3 ; Saeedi M4, 5 ; Karimpourrazkenari E5 ; Edraki N6 ; Sharifzadeh M7 ; Khanavi M8 ; Akbarzadeh T1, 5
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  7. 7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Bioorganic Chemistry Published:2019


Abstract

A new series of tacrine-coumarin hybrids linked to 1,2,3-triazole were designed, synthesized, and tested as potent dual binding site cholinesterase inhibitors (ChEIs) for the treatment of Alzheimer's disease (AD). Among them, compound 8e was the most potent anti-AChE derivative (IC 50 = 27 nM) and compound 8m displayed the best anti-BChE activity (IC 50 = 6 nM) much more active than tacrine and donepezil as the reference drugs. Compound 8e was also evaluated for its BACE1 inhibitory activity and neuroprotectivity against PC12 cells exposed to Aβ 25-35 which indicated low activity. Finally, in vivo studies by Morris water maze task showed that compound 8e significantly reversed scopolamine-induced memory deficit in rats. © 2018
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