Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer’s disease therapy

Eva Ramos; Alejandra Palomino-Antolín; Manuela Bartolini; Isabel Iriepa; Ignacio Moraleda; Daniel Diez-Iriepa; Abdelouahid Samadi; Carol V. Cortina; Mourad Chioua; Javier Egea; Alejandro Romero; José Marco-Contelles

doi:10.3390/molecules24081503

Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer’s disease therapy

Eva Ramos
, Alejandra Palomino-Antolín
, Manuela Bartolini
, Isabel Iriepa
, Ignacio Moraleda
, Daniel Diez-Iriepa
, Abdelouahid Samadi
, Carol V. Cortina
, Mourad Chioua
, Javier Egea
, Alejandro Romero
, José Marco-Contelles

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 µM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC₅₀ (hAChE) = 22.0 ± 1.3 µM; IC₅₀ (hBuChE) = 6.79 ± 0.33 µM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer’s disease.

Original language	English
Article number	1503
Journal	Molecules
Volume	24
Issue number	8
DOIs	https://doi.org/10.3390/molecules24081503
Publication status	Published - Apr 17 2019

Keywords

Alzheimer’s disease
Cholinesterase inhibitor
Hepatotoxicity
Molecular modeling
Neuroprotection
Quinoxalines
Quinoxalinetacrines
Tacrine

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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10.3390/molecules24081503

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title = "Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer{\textquoteright}s disease therapy",

abstract = "We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer{\textquoteright}s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 µM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 ± 1.3 µM; IC50 (hBuChE) = 6.79 ± 0.33 µM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer{\textquoteright}s disease.",

keywords = "Alzheimer{\textquoteright}s disease, Cholinesterase inhibitor, Hepatotoxicity, Molecular modeling, Neuroprotection, Quinoxalines, Quinoxalinetacrines, Tacrine",

author = "Eva Ramos and Alejandra Palomino-Antol{\'i}n and Manuela Bartolini and Isabel Iriepa and Ignacio Moraleda and Daniel Diez-Iriepa and Abdelouahid Samadi and Cortina, \{Carol V.\} and Mourad Chioua and Javier Egea and Alejandro Romero and Jos{\'e} Marco-Contelles",

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day = "17",

doi = "10.3390/molecules24081503",

language = "English",

volume = "24",

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T1 - Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer’s disease therapy

AU - Ramos, Eva

AU - Palomino-Antolín, Alejandra

AU - Bartolini, Manuela

AU - Iriepa, Isabel

AU - Moraleda, Ignacio

AU - Diez-Iriepa, Daniel

AU - Samadi, Abdelouahid

AU - Cortina, Carol V.

AU - Chioua, Mourad

AU - Egea, Javier

AU - Romero, Alejandro

AU - Marco-Contelles, José

PY - 2019/4/17

Y1 - 2019/4/17

N2 - We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 µM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 ± 1.3 µM; IC50 (hBuChE) = 6.79 ± 0.33 µM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer’s disease.

AB - We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer’s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 µM to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 ± 1.3 µM; IC50 (hBuChE) = 6.79 ± 0.33 µM). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer’s disease.

KW - Alzheimer’s disease

KW - Cholinesterase inhibitor

KW - Hepatotoxicity

KW - Molecular modeling

KW - Neuroprotection

KW - Quinoxalines

KW - Quinoxalinetacrines

KW - Tacrine

UR - https://www.scopus.com/pages/publications/85064854798

UR - https://www.scopus.com/pages/publications/85064854798#tab=citedBy

U2 - 10.3390/molecules24081503

DO - 10.3390/molecules24081503

M3 - Article

C2 - 30999586

AN - SCOPUS:85064854798

SN - 1420-3049

VL - 24

JO - Molecules

JF - Molecules

IS - 8

M1 - 1503

ER -

Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer’s disease therapy

Abstract

Keywords

ASJC Scopus subject areas

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