Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent
| العنوان: | Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent |
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| المؤلفون: | Orsolya Huzian, Ramóna Madácsi, Gábor J. Szebeni, László G. Puskás, Iván Kanizsai, Róbert Alföldi, Márió Gyuris, László Hackler, Levente Knapp |
| المصدر: | Molecules Volume 24 Issue 23 |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Quinidine, Pharmaceutical Science, 01 natural sciences, Article, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, 8-hydroxyquinoline, mitochondrial membrane potential, cytoprotection, Cell Line, Tumor, Drug Discovery, medicine, Humans, enantioselective synthesis, Physical and Theoretical Chemistry, Membrane potential, Membrane Potential, Mitochondrial, Quinine, 010405 organic chemistry, Chemistry, Protein Stability, Gene Expression Profiling, Betti reaction, Organic Chemistry, Neurodegeneration, In vitro toxicology, neurodegeneration, Stereoisomerism, Cell sorting, HIF1A, medicine.disease, Flow Cytometry, Hypoxia-Inducible Factor 1, alpha Subunit, Oxyquinoline, Cytoprotection, 0104 chemical sciences, Oxidative Stress, Biochemistry, Gene Expression Regulation, Chemistry (miscellaneous), Hydroxyquinolines, Molecular Medicine, Protein stabilization, Alzheimer’s disease, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Hypoxia is a common feature of neurodegenerative diseases, including Alzheimer&rsquo 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1420-3049 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69f6b077b776a4cadbf208add50ecebe https://pubmed.ncbi.nlm.nih.gov/31771153 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....69f6b077b776a4cadbf208add50ecebe |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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