Antihypoxic activity of adaptaquin enantiomers
- Авторы: Gaisina I.N.1, Khristichenko A.Y.2, Gaisin A.M.1, Smirnova N.A.2, Gazaryan I.G.2,3, Poloznikov A.A.2,4
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Учреждения:
- Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago
- Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
- Department of Chemistry, M. V. Lomonosov Moscow State University
- National Radiological Medical Research Center, Ministry of Healthcare of the Russian Federation
- Выпуск: Том 67, № 12 (2018)
- Страницы: 2320-2322
- Раздел: Brief Communications
- URL: https://ogarev-online.ru/1066-5285/article/view/243237
- DOI: https://doi.org/10.1007/s11172-018-2376-0
- ID: 243237
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Аннотация
Adaptaquin, 7-{(4-chlorophenyl)[(3-hydroxypyridin-2-yl)amino]methyl}quinolin-8-ol (1), was identified in our earlier study as a hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor by high-throughput screening of cell lines, which stably express the reporter construct encoding a fusion protein composed of the HIF oxygen degradable domain and firefly luciferase (HIF1 ODD-luc). Adaptaquin is a specific inhibitor of this enzyme and exhibits neuroprotective properties in cell models of oxidative stress and in vivo models of hemorrhagic stroke. The role of the chiral carbon atom in the inhibitor molecule was studied in order to further improve the adaptaquin structure. The separation into two enantiomers was performed. Both enantiomers were shown to equally activate the HIF1 ODD-luc reporter. The adaptaquin structure can be significantly modified and made more sophisticated in order to improve specificity toward this group of enzymes and subsequently toward individual isozymes.
Об авторах
I. Gaisina
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago
Email: andrey.poloznikov@nmicr.ru
США, 833 South Wood, Chicago, IL, 60612
A. Khristichenko
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
Email: andrey.poloznikov@nmicr.ru
Россия, 1 ul. Samory Mashela, Moscow, 117997
A. Gaisin
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago
Email: andrey.poloznikov@nmicr.ru
США, 833 South Wood, Chicago, IL, 60612
N. Smirnova
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
Email: andrey.poloznikov@nmicr.ru
Россия, 1 ul. Samory Mashela, Moscow, 117997
I. Gazaryan
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology; Department of Chemistry, M. V. Lomonosov Moscow State University
Email: andrey.poloznikov@nmicr.ru
Россия, 1 ul. Samory Mashela, Moscow, 117997; Bld. 3, 1 Leninskie Gory, Moscow, 119991
A. Poloznikov
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology; National Radiological Medical Research Center, Ministry of Healthcare of the Russian Federation
Автор, ответственный за переписку.
Email: andrey.poloznikov@nmicr.ru
Россия, 1 ul. Samory Mashela, Moscow, 117997; 4 ul. Koroleva, Obninsk, 249036
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