Objective. The article is devoted to study the anti-hypoxemic properties of new coumarin derivatives in the models of hypoxemic hypoxia with hypercapnia, hemic hypoxia and histotoxic hypoxia. Materials and methods. Нypoxemic hypoxia with hypercapnia was modeled as follows: mice were placed in hermetic 200 cm3 jars one in a jar. Hemic hypoxia was reproduced in mice by single subcutaneous introduction of sodium nitrite in a dose of 230 mg/kg. Histotoxic hypoxia was caused in mice by intraperitoneal introduction of sodium nitroprusside in a dose of 20 mg/kg. Coumarin derivatives under lab codes IEM-2266 and IEM-2267 were dissolved in distilled water with addition of twin-80, and then a single intraperitoneal infusion of them in doses 25 and 50 mg/kg was made 45 minutes before placing to the model conditions. Increased life time of an animal compared with the control served the criterion of anti-hypoxemic effect of the studied substances. Results. In hypoxemic hypoxia with hypercapnia test compound under IEM-2267 in doses of 25 and 50 mg/kg increased mice life time by 26 and 34% respectively in comparison with control. In hemic hypoxia model, the positive effect was seen with IEM-2266 compound in a dose of 50 mg/kg which increased life time of animals by 45% in comparison with control. In histotoxic hypoxia model, at preventive introduction of IEM-2266 compound in a dose of 25 mg/kg and IEM-2267 in a dose of 50 mg/kg life time increased up to 117% and 123% respectively. Conclusion. The coumarin derivatives IEM-2266 and IEM-2267 relieved the course of acute hypoxia and increased life time of animals in the models of hypoxemic hypoxia with hypercapnia, hemic hypoxia and histotoxic hypoxia.
Introduction. A study of the effects of coumarins has not received widespread use in medicine, largely due to the lack of optimal dosage forms, the creation of which is complicated by their poor solubility in water. Currently, studies are underway on the synthesis of macromolecules, combining various structural fragments, which will lead to increased biological activity of the synthesized coumarin derivatives compared to natural coumarins. The aim of this work was to study the central effect of new coumarin-based compounds: IEM-2262, IEM-2263, IEM-2266, IEM-2267 on emotional and research behavior in rats. Methods. Studies have been carried out using battery of tests that are commonly used to study emotional and exploratory behavior: an open field test and an elevated plus maze in rats. The neuroprotector mexidol (200 mg/kg i.p., Farmasoft, Russia) was used as a reference substance. Results. Coumarins (1050 mg/kg ip) have been shown to have a mild psychotropic, predominantly anti-anxiety and sedative effect. 7-Alkoxycoumarins (IEM-2262 and IEM-2266) and 4-aminocoumarins (IEM-2263 and IEM-2267) have different sensitivity in the open field compared with the effects in the elevated plus maze. Anxiolytic properties appeared in the elevated plus maze after the administration of 4-aminocoumarins (IEM-2263 and IEM-2267). The number of defecation boluses in the open field decreased as a result of the administration of 7-alkoxycoumarins (IEM-2262), which was associated not only with fear of novelty, but to a greater extent with anti-stress action. Thus, the new coumarin derivatives have mild tranquilizing and anti-stress effects and can be used in the future for post-traumatic stress disorders with panic attacks.
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 200220 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.