Effects of fullerene C60 with antihypoxants

Abstract

BACKGROUND: Drug improvement is often carried out with the help of chemical modifications that improve the receptor action or transport of drugs to their target tissues.

AIM: The aim of this study was to investigate the effect of combinations of C₆₀ fullerene with amtizol, 2-amino-4-acetylthiazolo[5,4-b]indole, metaprot, metaprot base, and rutin on antihypoxic activities in a model of acute hypoxia with hypercapnia.

MATERIALS AND METHODS: Several compounds with mono-, bi-, and tricyclic structures were examined separately or combined with C60 fullerene. All compounds, except for rutin, were synthesized at the Department of Pharmacology of the S.M. Kirov Military Medical Academy and contain active amino groups, nitrogen, and sulfur atoms in the cycles: amtizol (3,5-diamino-1,2,4-thiadiazole), VM-606 (2-amino-4-acetylthiazolo[5,4-b]indole), Metaprot (2-ethylthiobenzimidazole hydrobromide monohydrate), and Metaprot base. All compounds demonstrated antihypoxic activity. Hypobaric hypoxia was simulated in a flow pressure chamber by “lifting” animals to a height of 10,000 m at a speed of 50 m/s and exposure for 60 min. The preparations were administered intraperitoneally 60 min before the experiment. The protective effect was evaluated by the average life expectancy at altitude. Hypoxia with hypercapnia was assessed on male white mice weighing 20–22 g, which were placed in 200 mL glass jars with hermetic lids, which were lowered under water to prevent air leakage. The studied preparations and their complexes with fullerene in the form of a thin suspension with Tween-80 were administered intraperitoneally min before hypoxia. The lifespan of the animals was recorded.

RESULTS: The formation of the complex and its properties depend on the development of a donor–acceptor bond between the drug and fullerene. An increase in the bioavailability of amtizol in the form of a complex with C₆₀ fullerene increased the antihypoxic activity of the mixture by 40%. For the first time, dynamic curves of the activities of amtizol and 2-amino-4-acetylthiazolo[5,4-b]indole depending on time were obtained in a model of hypercapnic hypoxia.

CONCLUSION: Fullerene C₆₀ enhances the antihypoxic activity of the studied compounds due to an increase in the bioavailability of the antihypoxant caused by the microporation of tissue membranes due to the action of fullerene C₆₀.

Keywords

C60 fullerene / antihypoxants / amtizol / 2-amino-4-acetylthiazolo[5,4-b]indole / Metaprot / Metaprot base / rutin / hypoxia with hypercapnia / bioavailability

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