Synthesis, Biological Assessment and Molecular Modeling of Racemic QuinoPyranoTacrines for Alzheimer's Disease Therapy
| Autor: | Jana Janockova, Ondrej Soukup, Daniel Jun, Mourad Chioua, José Marco-Contelles, Ignacio Moraleda, Lhassane Ismaili, Vendula Sepsova, Fakher Chabchoub, Isabel Iriepa, Hélène Martin, Youssef Dgachi, Estefanía Serrano |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Molecular Modeling General Chemistry Management Synthesis 03 medical and health sciences Disease therapy 030104 developmental biology 0302 clinical medicine Political science QuinoPyranoTacrines Military health Cost action Biological Evaluation Alzheimer’s disease 030217 neurology & neurosurgery Biological evaluation |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 2365-6549 0017-9906 |
| Popis: | In this report we describe the synthesis, biological evaluation and molecular modeling of new tacrine analogues such as QuinoPyranTacrines (QPTs), designed by juxtaposition of 1,4- naphthoquinone and tacrine. From these results we have identified QPT16 as a permeable, selective human acetylcholinesterase inhibitor [IC50= 1.1 0.15 mM], 3.5-fold less-hepatotoxic than tacrine at 1000 mM concentration, and consequently, a potential new hit-compound for further investigation targeted to find a new agent for AD therapy. LI thanks the Regional Council of Franche-Comte (2016YC-04540 and 04560) for financial support. OS thanks Faculty of Military Health Sciences, University of Defence, MH CZ – DRO (UHHK, 00179906) and by Long Term Development Plan – 1011 for support. JMC thank MINECO (Spain) for grant SAF2015-65586-R, and EU (COST Action CA15135: “Multi-target paradigm for innovative ligand identification in the drug discovery process”) for support. |
| Databáze: | OpenAIRE |
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