Antihypoxic effect of new synthetic derivatives of 7-alkoxycoumarin and 4-aminocoumarin in acute hypobaric hypoxia in rats
- Authors: Kashirin A.O.1, Krylova I.B.1, Selina E.N.1, Polukeev V.A.1, Zarubina I.V.1, Bychkov E.R.1, Shabanov P.D.1
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Affiliations:
- Institute of Experimental Medicine
- Issue: Vol 19, No 4 (2021)
- Pages: 413-420
- Section: Original articles
- URL: https://journals.eco-vector.com/RCF/article/view/100031
- DOI: https://doi.org/10.17816/RCF194413-420
- ID: 100031
Cite item
Abstract
BACKGROUND: Coumarins are naturally occurring molecules with a wide range of pharmacological activities. Their use is limited by difficulties in isolation from plant material, toxicity, and low solubility. The chemical structure of these compounds makes coumarins promising for the synthesis of a large number of derivatives that may have biological activity and be of interest as potential drugs. We had synthesized coumarin derivatives, two of which – IEM-2266 (7-alkoxycoumarin derivative) and IEM-2267 (4-aminocoumarin derivative) – have shown antihypoxic effect in mice in models of hypoxic hypoxia with hypercapnia, histotoxic and hemic hypoxia.
AIM: The aim of this work was to study the antihypoxic effect of new coumarin derivatives IEM-2266 and IEM-2267 under conditions of acute hypobaric hypoxia in rats.
METHODS: The experimental work was performed on male Wistar rats weighing 200–220 g. Acute hypobaric hypoxia was induced in rats by placing them in a flow pressure chamber. Compounds IEM-2266 and IEM-2267 were administered intraperitoneally at the dose 25 mg/kg once 50 minutes before hypoxia. Mexidol® at the dose of 100 mg/kg was used as a reference drug. The antihypoxic activity of the substances was assessed according to the following indicators: 1) lifespan at the critical height 11,000 m; 2) the value of the individual high-altitude threshold; 3) individual resistance to hypoxia calculated from high-altitude threshold, expressed in points; 4) survival at consistently presented heights; 5) determination of the structure of population resistance according to the ratio of animals with low, medium and high resistance to hypoxia.
RESULTS: New coumarin derivatives IEM-2266 and IEM-2267 exhibited antihypoxic activity under acute hypobaric hypoxia conditions. With the use of IEM-2266, IEM-2267, and Mexidol, the lifespan of animals at a critical altitude of 11,000 m increased by 2.4, 5.4, and 4.9 times, respectively, compared with the control, the point based assessment of individual resistance to hypoxia increased by 36, 66 and 67%, the absolute value of high-altitude threshold increased significantly (p < 0.05). Coumarin derivatives changed the structure of population resistance, increasing the proportion of highly resistant animals.
CONCLUSIONS: Thus, the effect of IEM-2267 is comparable, and even exceeds the effect of Mexidol. The 7-alkoxycoumarin derivative IEM-2266 has a moderate, and the 4-aminocoumarin derivative IEM-2267 has high antihypoxic activity in rat AHbH conditions.
Full Text
About the authors
Anton O. Kashirin
Institute of Experimental Medicine
Author for correspondence.
Email: kashirin.anton@mail.ru
Postgraduate student
Russian Federation, 12, Academika Pavlova st., Saint Petersburg, 197376Irina B. Krylova
Institute of Experimental Medicine
Email: irinakrylova@mail.ru
SPIN-code: 7478-0420
Cand. Sci. (Biol.), Senior Researcher
Russian Federation, 12, Academika Pavlova st., Saint Petersburg, 197376Elena N. Selina
Institute of Experimental Medicine
Email: selina.elena@mail.ru
ORCID iD: 0000-0003-4591-209X
SPIN-code: 5558-2731
Researcher
Russian Federation, 12, Academika Pavlova st., Saint Petersburg, 197376Valery A. Polukeev
Institute of Experimental Medicine
Email: cyclic@peterlink.ru
SPIN-code: 6843-8295
Junior Researcher
Russian Federation, 12, Academika Pavlova st., Saint Petersburg, 197376Irina V. Zarubina
Institute of Experimental Medicine
Email: I.V.Zarubina@inbox.ru
Dr. Sci. Biol. (Pharmacology), Professor, Senior Researcher
Russian Federation, 12, Academika Pavlova st., Saint Petersburg, 197376Evgenii R. Bychkov
Institute of Experimental Medicine
Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN-code: 9408-0799
Cand. Sci. (Med.)
Russian Federation, 12, Academika Pavlova st., Saint Petersburg, 197376Petr D. Shabanov
Institute of Experimental Medicine
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477
Dr. Sci. (Med.), Professor
Russian Federation, 12, Academika Pavlova st., Saint Petersburg, 197376References
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