Next Article in Journal
Eggplant Germination is Promoted by Hydrogen Peroxide and Temperature in an Independent but Overlapping Manner
Next Article in Special Issue
Antifungal Styryloquinolines as Candida albicans Efflux Pump Inhibitors: Styryloquinolines are ABC Transporter Inhibitors
Previous Article in Journal
Purification and Product Characterization of Lipoxygenase from Opium Poppy Cultures (Papaver somniferum L.)
Previous Article in Special Issue
8-Hydroxyquinoline Glycoconjugates: Modifications in the Linker Structure and Their Effect on the Cytotoxicity of the Obtained Compounds
 
 
Article

Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent

1
Avidin Ltd., 6726 Szeged, Hungary
2
Avicor Ltd., 6726 Szeged, Hungary
3
Aperus Pharma Co. Ltd., 6726 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Academic Editor: Robert Musioł
Molecules 2019, 24(23), 4269; https://doi.org/10.3390/molecules24234269
Received: 5 November 2019 / Revised: 19 November 2019 / Accepted: 20 November 2019 / Published: 23 November 2019
(This article belongs to the Special Issue Synthesis and Application of Quinolines and Quinoline Derivatives)
Hypoxia is a common feature of neurodegenerative diseases, including Alzheimer’s disease that may be responsible for disease pathogenesis and progression. Therefore, the hypoxia-inducible factor (HIF)1 system, responsible for hypoxic adaptation, is a potential therapeutic target to combat these diseases by activators of cytoprotective protein induction. We have selected a candidate molecule from our cytoprotective hydroxyquinoline library and developed a novel enantioselective synthesis for the production of its enantiomers. The use of quinidine or quinine as a catalyst enabled the preparation of enantiomer-pure products. We have utilized in vitro assays to evaluate cytoprotective activity, a fluorescence-activated cell sorting (FACS) based assay measuring mitochondrial membrane potential changes, and gene and protein expression analysis. Our data showed that the enantiomers of Q134 showed potent and similar activity in all tested assays. We have concluded that the enantiomers exert their cytoprotective activity via the HIF1 system through HIF1A protein stabilization. View Full-Text
Keywords: 8-hydroxyquinoline; Alzheimer’s disease; Betti reaction; enantioselective synthesis; cytoprotection; neurodegeneration; mitochondrial membrane potential; HIF1A 8-hydroxyquinoline; Alzheimer’s disease; Betti reaction; enantioselective synthesis; cytoprotection; neurodegeneration; mitochondrial membrane potential; HIF1A
Show Figures

Graphical abstract

MDPI and ACS Style

Hackler, L., Jr.; Gyuris, M.; Huzián, O.; Alföldi, R.; Szebeni, G.J.; Madácsi, R.; Knapp, L.; Kanizsai, I.; Puskás, L.G. Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent. Molecules 2019, 24, 4269. https://doi.org/10.3390/molecules24234269

AMA Style

Hackler L Jr., Gyuris M, Huzián O, Alföldi R, Szebeni GJ, Madácsi R, Knapp L, Kanizsai I, Puskás LG. Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent. Molecules. 2019; 24(23):4269. https://doi.org/10.3390/molecules24234269

Chicago/Turabian Style

Hackler, László, Jr., Márió Gyuris, Orsolya Huzián, Róbert Alföldi, Gábor J. Szebeni, Ramóna Madácsi, Levente Knapp, Iván Kanizsai, and László G. Puskás. 2019. "Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent" Molecules 24, no. 23: 4269. https://doi.org/10.3390/molecules24234269

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop