Russian Chemical Bulletin

, Volume 67, Issue 12, pp 2320–2322 | Cite as

Antihypoxic activity of adaptaquin enantiomers

  • I. N. Gaisina
  • A. Yu. Khristichenko
  • A. M. Gaisin
  • N. A. Smirnova
  • I. G. Gazaryan
  • A. A. PoloznikovEmail author
Brief Communications


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.

Key words

oxyquinoline structure-activity relationship reporter assay HIF prolyl hydroxylase inhibitor 


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • I. N. Gaisina
    • 1
  • A. Yu. Khristichenko
    • 2
  • A. M. Gaisin
    • 1
  • N. A. Smirnova
    • 2
  • I. G. Gazaryan
    • 2
    • 3
  • A. A. Poloznikov
    • 2
    • 4
    Email author
  1. 1.Department of Medicinal Chemistry and PharmacognosyUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Dmitry Rogachev National Medical Research Center of Pediatric HematologyOncology and ImmunologyMoscowRussian Federation
  3. 3.Department of ChemistryM. V. Lomonosov Moscow State UniversityMoscowRussian Federation
  4. 4.National Radiological Medical Research CenterMinistry of Healthcare of the Russian FederationObninskRussian Federation

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