2. Academic Validation
  3. New tacrine-derived AChE/BuChE inhibitors: Synthesis and biological evaluation of 5-amino-2-phenyl-4H-pyrano[2,3-b]quinoline-3-carboxylates

New tacrine-derived AChE/BuChE inhibitors: Synthesis and biological evaluation of 5-amino-2-phenyl-4H-pyrano[2,3-b]quinoline-3-carboxylates

  • Eur J Med Chem. 2017 Mar 10:128:237-246. doi: 10.1016/j.ejmech.2017.01.042.
Mohammad Eghtedari 1,  Yaghoub Sarrafi 2,  Hamid Nadri 3,  Mohammad Mahdavi 4,  Alireza Moradi 3,  Farshad Homayouni Moghadam 5,  Saeed Emami 6,  Loghman Firoozpour 4,  Ali Asadipour 7,  Omid Sabzevari 8,  Alireza Foroumadi 9
Affiliations

Affiliations

  • 1 Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.
  • 2 Faculty of Chemistry, University of Mazandaran, Babolsar, Iran. Electronic address: ysarrafi@umz.ac.ir.
  • 3 Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
  • 4 Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
  • 5 Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
  • 6 Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
  • 7 Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
  • 8 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 9 Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aforoumadi@yahoo.com.
PMID: 28189905 DOI: 10.1016/j.ejmech.2017.01.042
Abstract

A series of poly-functionalized tacrine-derived compounds namely 5-amino-2-phenyl-4H-pyrano[2,3-b]quinoline-3-carboxylates were designed and synthesized as cholinesterases inhibitors. The in vitro inhibition assay against AChE and BuChE demonstrated that most of compounds had potent AChE inhibitory with reserving potential of BuChE inhibition. Among them, compound 6i bearing a 4-(3-bromophenyl) moiety showed the most potent activity against AChE/BuChE (IC50s values of 0.069 and 1.35 μM, respectively). The anti-AChE activity of 6i was five times more than that of tacrine. The SAR study revealed that chloro/bromo substituent at ortho or meta position of the 4-phenyl ring can improve the anticholinesterase activity.

Keywords

Acetylcholinesterase; Alzheimer's disease; Butyrylcholinesterase; Tacrine.

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