Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer’s Disease Therapy - Archive ouverte HAL Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2020

Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer’s Disease Therapy

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Óscar Bautista-Aguilera
Mourad Chioua
  • Function : Author
Rudolf Andrys
  • Function : Author
Monika Schmidt
Petr Bzonek
María Ángeles Martínez-Grau
  • Function : Author
Christopher Beadle
  • Function : Author
Tatiana Vetman
  • Function : Author
Francisco López-Muñoz
Isabel Iriepa
Bernard Refouvelet
  • Function : Author
Kamil Musilek
José Marco-Contelles

Abstract

In this communication, we report the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer’s disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 µM), with Ki value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation.

Dates and versions

hal-03654611 , version 1 (28-04-2022)

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Óscar Bautista-Aguilera, Lhassane Ismaili, Mourad Chioua, Rudolf Andrys, Monika Schmidt, et al.. Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer’s Disease Therapy. International Journal of Molecular Sciences, 2020, 21 (11), pp.3913. ⟨10.3390/ijms21113913⟩. ⟨hal-03654611⟩

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