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Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, and Antioxidant Agents for Alzheimer's Disease Therapy.

ABSTRACT: Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1-one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a selective but moderately potent EeAChE inhibitor (IC50 = 38.7 ± 1.7 ?M), and a very potent antioxidant agent on the basis of the ORAC test (2.31 ± 0.29 ?mol·Trolox/?mol compound).

SUBMITTER: Boulebd H

PROVIDER: S-EPMC6273229 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Imidazopyranotacrines as Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, and Antioxidant Agents for Alzheimer's Disease Therapy.

Boulebd Houssem H Ismaili Lhassane L Bartolini Manuela M Bouraiou Abdelmalek A Andrisano Vincenza V Martin Helene H Bonet Alexandre A Moraleda Ignacio I Iriepa Isabel I Chioua Mourad M Belfaitah Ali A Marco-Contelles José J

Molecules (Basel, Switzerland) 20160324 4

Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1-one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a selective but moderately potent EeAChE inhibitor (IC50 = 38.7 ± 1.7 μM), and a very potent antioxidant agent ...[more]

PMID: 27023499

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