Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles
The aim. To study the acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles.Materials and methods. The study was performed on white laboratory female BALB/c mice (n=57) and male C57Bl/6 mice (n=66). Acute toxicity was assessed accordin...
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Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute
2025-07-01
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| Series: | Фармация и фармакология (Пятигорск) |
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| Online Access: | https://www.pharmpharm.ru/jour/article/view/1668 |
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| author | O. A. Puchenkova O. V. Shheblykina D. A. Kostina A. A. Bolgov P. R. Lebedev V. V. Molchanov T. G. Pokrovskaya M. V. Korokin E. A. Nikiforov N. F. Vaskina T. A. Idrisov T. D. Moseev V. V. Melekhin M. V. Varaksin V. N. Charushin O. N. Chupakhin |
| author_facet | O. A. Puchenkova O. V. Shheblykina D. A. Kostina A. A. Bolgov P. R. Lebedev V. V. Molchanov T. G. Pokrovskaya M. V. Korokin E. A. Nikiforov N. F. Vaskina T. A. Idrisov T. D. Moseev V. V. Melekhin M. V. Varaksin V. N. Charushin O. N. Chupakhin |
| author_sort | O. A. Puchenkova |
| collection | DOAJ |
| description | The aim. To study the acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles.Materials and methods. The study was performed on white laboratory female BALB/c mice (n=57) and male C57Bl/6 mice (n=66). Acute toxicity was assessed according to the interstate standard GOST 32644-2014 with histological evaluation of internal organs. Endothelial dysfunction was modeled by 7-day intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME). The studied small molecules were administered intragastrically using a probe. To assess the endothelial protective effect, the levels of systolic and diastolic blood pressure were evaluated, as well as the coefficient of endothelial dysfunction; for the cardioprotective effect, the results of stress tests on the myocardium were evaluated.Results. The study of acute toxicity of the studied small molecules allowed us to classify them as class 4 and 5. The administration of compounds 1(a–d) and 2(a–c) to mice at a dose equal to 1/10 of LD50 led to changes in blood pressure and restoration of the dynamics of pharmacological tests in response to the administration of acetylcholine and sodium nitroprusside. Molecules 1b and 2c showed statistically significant endothelial protective activity in 3 doses (1/10, 1/50 and 1/100 of LD50). Also, these hit compounds demonstrated cardioprotective effects, recorded by the restoration of the functional capabilities of the myocardium in response to load and in the adrenoreactivity test, and to a lesser extent, during resistance exercise.Conclusion. The studied compounds have low toxicity and have endothelial- and cardioprotective effects. This study may contribute to the formation of an idea about further directions in the study of the pharmacological activity of these molecules from the group of phenolic and thiophenolic derivatives of 2H-imidazoles. |
| format | Article |
| id | doaj-art-91acbd64b4d34683aedb7a056919d7e8 |
| institution | Kabale University |
| issn | 2307-9266 2413-2241 |
| language | Russian |
| publishDate | 2025-07-01 |
| publisher | Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute |
| record_format | Article |
| series | Фармация и фармакология (Пятигорск) |
| spelling | doaj-art-91acbd64b4d34683aedb7a056919d7e82025-08-20T03:44:21ZrusVolgograd State Medical University, Pyatigorsk Medical and Pharmaceutical InstituteФармация и фармакология (Пятигорск)2307-92662413-22412025-07-0112639440910.19163/2307-9266-2024-12-6-394-409529Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazolesO. A. Puchenkova0O. V. Shheblykina1D. A. Kostina2A. A. Bolgov3P. R. Lebedev4V. V. Molchanov5T. G. Pokrovskaya6M. V. Korokin7E. A. Nikiforov8N. F. Vaskina9T. A. Idrisov10T. D. Moseev11V. V. Melekhin12M. V. Varaksin13V. N. Charushin14O. N. Chupakhin15Belgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityBelgorod State National Research UniversityFederal University named after the First President of Russia B.N. YeltsinFederal University named after the First President of Russia B.N. YeltsinFederal University named after the First President of Russia B.N. YeltsinFederal University named after the First President of Russia B.N. Yeltsin1. Federal University named after the First President of Russia B.N. Yeltsin. 2. Ural State Medical University.1. Federal University named after the First President of Russia B.N. Yeltsin. 2. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences.1. Federal University named after the First President of Russia B.N. Yeltsin. 2. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences.1. Federal University named after the First President of Russia B.N. Yeltsin. 2. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences.The aim. To study the acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles.Materials and methods. The study was performed on white laboratory female BALB/c mice (n=57) and male C57Bl/6 mice (n=66). Acute toxicity was assessed according to the interstate standard GOST 32644-2014 with histological evaluation of internal organs. Endothelial dysfunction was modeled by 7-day intraperitoneal administration of N-nitro-L-arginine methyl ester (L-NAME). The studied small molecules were administered intragastrically using a probe. To assess the endothelial protective effect, the levels of systolic and diastolic blood pressure were evaluated, as well as the coefficient of endothelial dysfunction; for the cardioprotective effect, the results of stress tests on the myocardium were evaluated.Results. The study of acute toxicity of the studied small molecules allowed us to classify them as class 4 and 5. The administration of compounds 1(a–d) and 2(a–c) to mice at a dose equal to 1/10 of LD50 led to changes in blood pressure and restoration of the dynamics of pharmacological tests in response to the administration of acetylcholine and sodium nitroprusside. Molecules 1b and 2c showed statistically significant endothelial protective activity in 3 doses (1/10, 1/50 and 1/100 of LD50). Also, these hit compounds demonstrated cardioprotective effects, recorded by the restoration of the functional capabilities of the myocardium in response to load and in the adrenoreactivity test, and to a lesser extent, during resistance exercise.Conclusion. The studied compounds have low toxicity and have endothelial- and cardioprotective effects. This study may contribute to the formation of an idea about further directions in the study of the pharmacological activity of these molecules from the group of phenolic and thiophenolic derivatives of 2H-imidazoles.https://www.pharmpharm.ru/jour/article/view/1668azaheterocyclic compoundssmall moleculesendothelial dysfunctionimidazolesphenolsthiophenols |
| spellingShingle | O. A. Puchenkova O. V. Shheblykina D. A. Kostina A. A. Bolgov P. R. Lebedev V. V. Molchanov T. G. Pokrovskaya M. V. Korokin E. A. Nikiforov N. F. Vaskina T. A. Idrisov T. D. Moseev V. V. Melekhin M. V. Varaksin V. N. Charushin O. N. Chupakhin Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles Фармация и фармакология (Пятигорск) azaheterocyclic compounds small molecules endothelial dysfunction imidazoles phenols thiophenols |
| title | Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles |
| title_full | Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles |
| title_fullStr | Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles |
| title_full_unstemmed | Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles |
| title_short | Study of acute toxicity, endothelial- and cardioprotective properties of phenolic and thiophenolic derivatives of 2H-imidazoles |
| title_sort | study of acute toxicity endothelial and cardioprotective properties of phenolic and thiophenolic derivatives of 2h imidazoles |
| topic | azaheterocyclic compounds small molecules endothelial dysfunction imidazoles phenols thiophenols |
| url | https://www.pharmpharm.ru/jour/article/view/1668 |
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