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8-Hydroxyquinoline-based anti-Alzheimer multimodal agents

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Abstract

The concept of multitarget-directed ligands (MTDLs) has attracted considerable interest in the development of agents against Alzheimer’s disease. Cathepsin B, a cysteine protease, and butyrylcholinesterase, a serine hydrolase, play important function in the development and progression of Alzheimer’s disease. We present herein the evaluation of 8-hydroxyquinoline-based analogues with activities against butyrylcholinesterase and β-secretase activity of cathepsin B. Furthermore, inhibition of amyloid β aggregation, chelation of copper and zinc ions coupled with antioxidative properties and safe cytotoxicity profile of (1R,2S)-N-ethyl-2-[[(8-hydroxy-5-nitroquinolin-7-yl)methyl]amino]cyclohexane-1-carboxamide suggest that this derivative is a good starting point for optimization towards an effective multifunctional ligand.

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Acknowledgements

We thank Dr. Florian Nachon and Dr. Xavier Brazolloto (IBS, Grenoble, France and IRBA, Brétigny sur Orge, France) for providing us hAChE and hBChE. This study was supported by the Slovenian Research Agency (Projects L1-8157, Z3-9273, J4-8227 and J3-9267 and core financing P1-0208).

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia

    Damijan Knez, Izidor Sosič, Ana Mitrović, Anja Pišlar, Janko Kos & Stanislav Gobec

  2. Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia

    Janko Kos

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  1. Damijan Knez
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  2. Izidor Sosič
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Correspondence to Stanislav Gobec.

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Knez, D., Sosič, I., Mitrović, A. et al. 8-Hydroxyquinoline-based anti-Alzheimer multimodal agents. Monatsh Chem 151, 1111–1120 (2020). https://doi.org/10.1007/s00706-020-02651-0

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  • DOI: https://doi.org/10.1007/s00706-020-02651-0

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