2. Academic Validation
  3. Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors

Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and docking study of cholinesterase inhibitors

  • Eur J Med Chem. 2017 Jan 5:125:1200-1212. doi: 10.1016/j.ejmech.2016.11.008.
Zahra Najafi 1,  Mohammad Mahdavi 2,  Mina Saeedi 3,  Elahe Karimpour-Razkenari 4,  Raymond Asatouri 5,  Fahimeh Vafadarnejad 1,  Farshad Homayouni Moghadam 6,  Mahnaz Khanavi 7,  Mohammad Sharifzadeh 8,  Tahmineh Akbarzadeh 9
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 2 Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 3 Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 4 Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 5 Department of Biology, Science and Research Branch Islamic Azad, Tehran, Iran.
  • 6 Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
  • 7 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 8 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: msharifzadeh@tums.ac.ir.
  • 9 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: akbarzad@tums.ac.ir.
PMID: 27863370 DOI: 10.1016/j.ejmech.2016.11.008
Abstract

A new series of tacrine-1,2,3-triazole hybrids were designed, synthesized, and evaluated as potent dual cholinesterase inhibitors. Most of synthesized compounds showed good in vitro inhibitory activities toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, 7-chloro-N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5l) was found to be the most potent anti-AChE derivative (IC50 = 0.521 μM) and N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine (5j) demonstrated the best anti-BChE activity (IC50 = 0.055 μM). In vivo studies of compound 5l in Morris water maze task confirmed memory improvement in scopolamine-induced impairment. Also, molecular modeling and kinetic studies showed that compounds 5l and 5j bound simultaneously to the peripheral anionic site (PAS) and catalytic sites (CS) of the AChE and BChE.

Keywords

Alzheimer's disease; Cholinesterase; Docking study; Dual binding; Morris water maze; Tacrine-1,2,3-triazole.

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