title: New tacrine-derived AChE/BuChE inhibitors: Synthesis and biological evaluation of 5-amino-2-phenyl-4H-pyrano[2,3-b]quinoline-3-carboxylates.
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.
authors.affiliation: Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Eghtedari
authors.affiliation: Faculty of Chemistry, University of Mazandaran, Babolsar, Iran. Electronic address: ysarrafi@umz.ac.ir.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Sarrafi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mahdavi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
authors.forename: Farshad
authors.initials: F
authors.lastname: Homayouni Moghadam
authors.affiliation: Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Loghman
authors.initials: L
authors.lastname: Firoozpour
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Asadipour
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Sabzevari
authors.affiliation: 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.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D016716:PC12 Cells; D011714:Pyrans / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D011714:Pyrans; D011804:Quinolines; C000617033:ethyl 5-amino-4-(3-bromophenyl)-2-phenyl-6,7,8,9-tetrahydro-4H-pyrano(2,3-b)quinoline-3-carboxylate; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Butyrylcholinesterase; Tacrine